Antitumor activity of a recombinant soluble betaglycan in human breast cancer xenograft

We have demonstrated previously that ectopic expression of a soluble betaglycan, also known as transforming growth factor (TGF) beta type III receptor, can suppress the malignant properties of human carcinoma cells by antagonizing the tumor-promoting activity of TGF-beta (A. Bandyopadhyay et al., Cancer Res., 59: 5041-5046, 1999). In the current study, we investigated the potential therapeutic utility of a recombinant preparation of human and rat soluble betaglycan (sBG). Purified recombinant human sBG showed similar properties to its rat counterpart (M. M. Vilchis-Landeros et al., Biochem J., 355: 215-222, 2001). It bound TGF-beta with high affinity and isoform selectivity and neutralized the activity of TGF-beta(1) in two bioassays. Peritumoral (50 micro g/tumor, twice a week) or i.p. (100 micro g/animal, every alternate day) injection of sBG into human breast carcinoma MDA-MB-231 xenograft-bearing athymic nude mice significantly inhibited the tumor growth. The administration of sBG also reduced metastatic incidence and colonies in the lungs. The tumor-inhibitory activity of sBG was found to be associated with the inhibition of angiogenesis. Systemic sBG treatment significantly reduced tumor microvessel density detected with histological analyses and CD-31 immunostainings, as well as tumor blood volume measured with hemoglobin content. In an in vitro angiogenesis assay, treatment with the recombinant sBG significantly reduced the ability of human dermal microvascular endothelial cells to form a capillary tube-like structure on Matrigel. These findings support the conclusion that sBG treatment suppresses tumor growth and metastasis, at least in part by inhibiting angiogenesis. As such, it could be a useful therapeutic agent to antagonize the tumor-promoting activity of TGF-beta.     

A case of smouldering mastocytosis with peripheral blood eosinophilia and lymphadenopathy

Systemic mastocytosis (SM) is a clonal hematologic disease showing abnormal growth and accumulation of mast cells (MC) in visceral organs with or without skin involvement. The clinical course in SM is variable. In fact, indolent and aggressive variants have been described. In addition, SM patients may acquire an associated hematologic clonal non-MC lineage disease (AHNMD). In some cases, hematologic parameters are indicative of slowly progressing SM although the clinical course remains indolent over years. These cases have been referred to as smouldering SM. We report on a smouldering patient presenting with typical skin lesions, hypercellular marrow with focal MC aggregates, persistent leukocytosis (20,000-30,000/microl) with eosinophilia (5-10%), marked lymphadenopathy, and splenomegaly. The C-KIT mutation Asp-816-Val confirmed the diagnosis of SM. The clinical picture remained stable during an observation period of 10 years without signs of progression to an AHNMD or a high grade MC disease. These data show that some patients with SM can remain in a clinically indolent smouldering state over years even when presenting with marked eosinophilia and lymphadenopathy.     

Fatal occupational electrocutions in the United States

INTRODUCTION: The highest proportions of fatal occupational electrocutions have occurred among those employed in the electrical trades and in the construction and manufacturing industries. METHODS: Data from 1992 through 1999 were obtained from the Bureau of Labor Statistics Census of Fatal Occupational Injuries. RESULTS: Occupational electrocution deaths occurred almost entirely among males, with the highest rates among those aged 20-34 and among whites and American Indians. They were highest during the summer months, in the South, and in establishments employing 10 or fewer workers. The highest rates occurred in the construction, mining, and agriculture, forestry, and fishing industries and among trades associated with these industries. CONCLUSIONS: Electrocution continues to be a significant cause of occupational death. Workers need to be provided with safety training and employers, particularly smaller employers, persuaded of the need for safety training.     

Laparoscopic biliary surgery

The following article briefly sets out the possible new protocols that can be applied in biliary pathology, arising from the changes brought about by the appearance of new techniques of laparoscopic biliary surgery. It offers a synthesis of the latest and most novel articles on surgical technique and management in different biliary pathologies such as choledocholithiasis and cholecystitis. It can be concluded that management will differ greatly, depending on the technical capacities of the centre that is called upon to deal with one of these pathologies. A standard protocol for everybody cannot thus be established at present. The differences between endoscopic retrograde cholangiopancreatography and intraoperative laparoscopic cholangiography have still to be demonstrated, it is not possible to make generalisations about whether one technique is more useful than the other. The same could be said about whether access to the main biliary path should be achieved through the cystic conduct or whether, on the contrary, a choledochotomy should be performed.     

A retrospective epidemiological study on the association of bullous pemphigoid and neurological diseases

Bullous pemphigoid is a rare chronic recurrent dermatosis that is often reported in association with various neurological diseases. No investigation involving a large number of patients has ever been carried out to demonstrate such an association. This study was accomplished by analysing the discharge diagnosis of all hospitalized patients, both day-patients and inpatients, during a 5-year period (1995-2000) covering a total population group of 934,023 living in a region of Italy that has approximately 1,200,000 inhabitants. The results support the hypothesis of an association between bullous pemphigoid, multiple sclerosis and Parkinson's disease on a highly significant statistical basis. The aetiopathogenic mechanisms and the causes that induce the loss of immunological tolerance are not yet understood.     

CD25 indicates the neoplastic phenotype of mast cells: a novel immunohistochemical marker for the diagnosis of systemic mastocytosis (SM) in routinely processed bone marrow biopsy specimens

The diagnosis of systemic mastocytosis (SM) is based primarily on the histologic and immunohistochemical evaluation of a bone marrow trephine biopsy specimen. Although mast cell (MC) specific antigens like tryptase and chymase are detectable in routinely processed tissue, no immunohistochemical markers that can be used to discriminate between normal and neoplastic MCs are yet available. We have investigated the diagnostic value of an antibody against CD25 for the immunohistochemical detection of MCs in bone marrow sections in 73 patients with SM and 75 control cases (reactive marrow, n = 54; myelogenous neoplasms, n = 21) and correlated the results with the presence of c-kit mutations. While MCs in almost all patients with SM (72 of 73) expressed CD25, none of the control samples contained CD25-positive MCs. Irrespective of the SM subtype, most of neoplastic MCs expressed CD25. In 3 patients with advanced MC disease, pure populations of neoplastic MCs were obtained and found to express CD25 mRNA by RT-PCR analysis. In addition, all patients with CD25-positive MCs contained c-kit mutations, while all control cases exhibited wild type c-kit. CD25 therefore appears to be a reliable immunohistochemical marker for the discrimination of neoplastic from normal/reactive MCs, with potential as a diagnostic tool in SM.     

The development of the sturgeon heart

This paper presents a sequential analysis of the development of the sturgeon (Acipenser naccarii) heart from the end of gastrulation to the early juvenile stages. At late neurulation, the heart appears as a straight, short tube located over the endoderm that forms the wall of the yolk sac, in front of the developing head. The heart axis is aligned with the axis of the developing head. Subsequently, the heart elongates and adopts a C-shape, and its axis becomes perpendicular to that of the head. Around the time of hatching, the heart loses the loop and appears as a mostly straight tube with the chambers arranged in a craniocaudal sequence: outflow tract, ventricle, atrium, and a small sinus venosus. During the first 4 days post-hatching (dph), the heart starts looping again, adopts a C-shape, and undergoes a counterclockwise movement that brings the atrium to the left of the outflow tract and the ventricle to a caudal position. Thus, a primary and a secondary cardiac loop occur in the sturgeon. Later, the atria come to occupy a middle position behind the outflow tract, and the sinus venosus shifts from a caudal to a dorsal position. A morphological arrangement similar to that found in adult sturgeons is attained in all specimens at days 7–9 dph. The external changes are accompanied by a series of internal modifications that include trabeculation (3–4 dph), development of endocardial cushions in the atrioventricular canal (4 dph) and in the conus arteriosus (3–4 dph), conus (22–24 dph) and atrioventricular (18–20 dph) valve formation, and development of the epicardium (4 dph) and the coronary vessels (10 dph). The main developmental features of the heart have been registered, and a basic body of information, which should be very useful in future developmental studies, has been established. Similarities and dissimilarities between the development of the sturgeon heart and that of other vertebrates are underscored.