Modulation of receptors for the colony-stimulating factor, CSF-1, by bacterial lipopolysaccharide and CSF-1

The ability of the mononuclear phagocyte-specific colony-stimulating factor, CSF-1, to down-regulate its receptor on peritoneal exudate macrophages (PEM) was examined. Because of the essentially irreversible binding of CSF-1 to its receptor at 2 degrees C, unoccupied cell surface receptors could be measured by rapidly cooling PEM to 2 degrees C and determining the amount of 125I-CSF-1 bound at this temperature. On incubation with 125I-CSF-1 at 37 degrees C more receptors were lost than could be accounted for by 125I-CSF-1 binding. This receptor loss, apparently caused by CSF-1 itself, was shown to be due in large part to the presence of contaminating lipopolysaccharide (LPS), which at 10 ng/ml was by itself able to cause complete loss of the CSF-1 receptors. LPS also induced loss of the insulin receptor by PEM. LPS did not cause apparent CSF-1 receptor loss by binding to the receptor or by stimulating the release of CSF-1 or substances which compete for the binding of 125I-CSF-1 to the receptor. However, LPS did stimulate release of factors by LPS responsive (C3H/HeN) PEM which caused CSF-1 receptor loss by LPS non-responsive (C3H/HeJ) PEM. In the absence of LPS induced effects, incubation of 125I-CSF-1 with PEM at 37 degrees C resulted in down-regulation of the CSF-1 receptors. The number of CSF-1 receptor sites down-regulated corresponded to the number of CSF-1 molecules that were cell-associated plus the number that were intracellularly degraded and released.     

Astrocytes and intracerebral immune responses

The astrocyte is the most abundant cell within the central nervous system (CNS). This cell subserves a multiplicity of important functions that contribute to the process of neural development as well as to the integrity of normal brain function. Adding to the already exhaustive list of capabilities, the astrocyte has now been demonstrated to function as an intracerebral antigen presenting cell. These findings are serving to revise our view of the brain as an immunoprivileged site and perhaps will shed some light on the pathogenetic mechanisms involved in a number of CNS disorders of immune dysregulation. In this review we provide some perspective on the regulatory mechanisms that influence astrocyte immune functions. Specifically, we address the role played by the major histocompatibility complex (MHC) antigens as well as adhesion molecules in the initiation of brain immune responses.     

Trichosporon beigelii endocarditis as a complication of peritoneovenous shunt

Trichosporon is a common cause of superficial mycotic infection but has rarely been associated with endocarditis. The case of a patient who had a peritoneovenous shunt for chronic intractable ascites due to Laennec liver cirrhosis is described. The shunt was revised on several occasions, and the last procedure was complicated by a draining skin sinus wound. To the authors' knowledge, this is the first reported case of Trichosporon endocarditis complicating a peritoneovenous shunt.     

Birth factors and laterality: Effects of birth order,parental age,and birth stress on four indices of lateral preference

As an alternative to genetic theories of handedness, some theorists have offered an environmental mechanism, associated with birth stress, for the appearance of left-handedness. They suggest that brain damage as a result of birth difficulties can lead to a switch in hand preference from the right side to the left side. Consequently, one should find more left-handers in groups where the probability of the occurrence of birth stress is greater. Three studies are presented which explore the laterality of not only hand but also foot, eye, and ear, in a total of 5161 individuals, in an attempt to assess any relationship to birth stress. Maternal age seems to predict deviations from dextrality, dependent on the sex of the offspring, while paternal age and birth order do not. The use of a direct measure of conditions predisposing toward birth stress suggests that these results depend on prenatal or perinatal environmental trauma rather than chromosomal factors.This research was supported by grants from the Medical Research Council of Canada and from the Natural Sciences and Engineering Research Council of Canada, and represents an equal and shared contribution of both authors.     

Dietary and nutrient intakes of 25 Ningerum (New Guinea) adult males at two times of the year

In nutritional studies of traditional societies, it is often assumed that dietary intakes are sufficiently homogeneous for dietary studies of short duration to be adequate for accurate assessment of group nutrient intake. The present study examines this assumption by considering food and nutrient intakes of 25 adult males in rural Papua New Guinea (PNG). Five-day weighed dietary intakes were carried out on each individual twice, with a 6-month interval between measurements. The two measurements corresponded to the times of year when the climate was wet and wetter. Energy intakes, at 167 and 169 kJ/kg body weight, were within the range of values reported by other authors for adult males in PNG. Intakes of protein, thiamin, riboflavin, niacin, and calcium were low, while intakes of iron and vitamins A and C were above WHO (FAO/WHO, 1974) recommended daily allowances. Energy and nutrient intakes did not vary between the two times of year, with two exceptions: vitamin C and iron. Intakes of foods and food types varied between wet and wetter times, however. Within- and between-subject coefficients of variation of intakes of energy and six nutrients were used to calculate sample sizes needed to obtain estimates of group intakes at different levels of reliability and number of days of dietary measurement. This varied with the nutrient under consideration and the time of year. At a given level of reliability, accurate estimates of carbohydrate intake could be obtained with smaller sample sizes and/or number of days of observation than for energy, protein, and vitamin C intakes. Longer periods or larger samples would have been needed for the estimation of group vitamin A, fat, and calcium intakes. © 1992 Wiley-Liss, Inc.     

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): diagnosis by fine-needle aspiration

Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare idiopathic proliferative disorder of histiocytes with characteristic morphologic features. We describe a case of SHML occurring in a 14-yr-old black male, in whom the diagnosis was made by fine-needle aspiration of a cervical lymph node. Cytologic features included increased numbers of large histiocytes associated with a polymorphous, cellular background composed of benign lymphocytes, plasma cells, and polymorphonuclear leukocytes. Lymphophagocytosis was a prominent feature. Extranodal involvement of the larynx was documented by surgical biopsy; there was no other extranodal disease. One year after diagnosis, the patient is clinically well, with no residual lymphadenopathy.     

Pulmonary artery trunk sarcoma: a clinicopathologic, ultrastructural, and immunohistochemical study of four cases

Pulmonary artery sarcomas are rare tumors that arise in the region of the bulbus cordis, the embryologic structure that gives rise to the pulmonary trunk. Nearly 100 cases have been reported in the literature, yet considerable debate exists regarding the histogenesis and biologic properties of these neoplasms. We report four additional cases in which ultrastructural and immunohistochemical studies demonstrated that these tumors contain cellular constituents with features of myofibroblastic, cartilaginous, and osteogenic differentiation. Polyphenotypic expression of several mesenchymal lineages suggests that the progenitor cell has pluripotential properties. Our findings and a review of the literature appear to confirm that pulmonary artery sarcomas are histopathologically heterogeneous, possibly reflecting the indeterminate character of the mesenchymal cell(s) of origin. The poor prognosis is attributable to the critical anatomic location of the neoplasm rather than its metastatic potential, which is low.     

Novel multi-component nanopharmaceuticals derived from poly(ethylene) glycol, retro-inverso-Tat nonapeptide and saquinavir demonstrate combined anti-HIV effects

Background  

Current anti-AIDS therapeutic agents and treatment regimens can provide a dramatically improved quality of life for HIV-positive people, many of whom have no detectable viral load for prolonged periods of time. Despite this, curing AIDS remains an elusive goal, partially due to the occurrence of drug resistance. Since the development of resistance is linked to, among other things, fluctuating drug levels, our long-term goal has been to develop nanotechnology-based drug delivery systems that can improve therapy by more precisely controlling drug concentrations in target cells. The theme of the current study is to investigate the value of combining AIDS drugs and modifiers of cellular uptake into macromolecular conjugates having novel pharmacological properties.