Constitutive secretion of the granule chymase mouse mast cell protease-1 and the chemokine, CCL2, by mucosal mast cell homologues

BACKGROUND: The mucosal mast cell (MMC) granule-specific beta-chymase, mouse mast cell protease-1 (mMCP-1), is released systemically into the bloodstream early in nematode infection before parasite-specific IgE responses develop and TGF-beta1 induces constitutive release of mMCP-1 by homologues of MMC in vitro. Intraepithelial MMC may also express the chemokine CCL2 (monocyte chemotactic protein-1) during nematode infection but the expression of this chemokine by MMC homologues has not been investigated. OBJECTIVE: To investigate the expression and to compare the mechanisms of constitutive release of the chymase, mMCP-1, and the chemokine, CCL2. METHODS: MMC homologues were generated by culturing bone marrow cells in the presence of TGF-beta1, IL-3, IL-9 and stem cell factor (SCF). The intracellular distribution of mMCP-1 and CCL2 was examined by confocal microscopy. The involvement of the Golgi complex and of protein synthesis in the constitutive release of mMCP-1 and CCL2 was investigated using the Golgi-disrupting agent brefeldin A and cycloheximide to block protein synthesis. Secreted analytes were quantified by ELISA. RESULTS: mMCP-1 colocalized with Golgi matrix protein 130 but was most abundant in the granules, whereas CCL2 was not found in the granules but appeared to be located uniquely in the Golgi complex. Extracellular release of mMCP-1 was significantly inhibited ( approximately 40%) by cycloheximide and by the Golgi-disrupting agent brefeldin A, indicating both continuous protein synthesis and transportation via the Golgi complex are required for optimal mMCP-1 secretion. A similar but more marked inhibitory effect with both compounds was demonstrated on the constitutive secretion of CCL2. CONCLUSION: The culture conditions that promote mMCP-1 expression and release by MMC homologues also promote the expression and release of CCL2. Constitutive release involves de novo protein synthesis and requires a functional Golgi complex, suggesting that similar mechanisms of extracellular secretion operate for both mediators.     

New concepts in the diagnosis and management of optic nerve sheath meningioma.

Optic nerve sheath meningiomas are by far the most common tumors of the optic nerve sheath. The diagnosis can be suspected in most cases from clinical findings and supported by the results of neuroimaging, obviating tissue biopsy in the majority of cases. Observation may be appropriate in patients with mild or no visual deficit or in whom visual loss is not progressing, whereas stereotactic fractionated radiation therapy has been demonstrated to improve or stabilize vision in progressive or advanced cases. Attempts at surgical excision, and even biopsy, of optic nerve sheath meningiomas are associated with a high risk of blindness and should be reserved for the rare case of an anteriorly located, primarily exophytic tumor with focal involvement of the dural sheath.     

Decline in human immunodeficiency virus seropositivity and seroconversion in US Navy enlisted personnel: 1986 to 1989. Navy HIV Working Group.

The US Navy administered 1,795,578 enzyme-linked immunosorbent assay (ELISA) tests to 848,632 active-duty Navy enlisted personnel during 1986 to 1989. This study identified 2438 human immunodeficiency virus (HIV)-seropositive active-duty enlisted Navy personnel, including 778 seroconverters. Three types of quarterly rates of HIV seropositivity and seroconversion were determined. All three rates declined. This decline could not be explained by changes in the population tested according to age, race, sex, occupation, or geographic location of home port.     

Detection of Mycoplasma and its antibodies in the blood of HIV-positive patients and in healthy persons]

The comparative study of HIV-positive and clinically healthy persons has indicated that the antigens of M. pneumoniae, M. fermentans and U. urealyticum are encountered nearly twice more frequently in the blood of HIV-infected patients than in that of healthy individuals. Mycoplasma antibodies are detected in HIV-positive persons 12 times more frequently than in healthy ones. Among the HIV-infected persons there are those who have simultaneously antigens of some Mycoplasma species.     

The hidden mortality in surgically treated necrotizing enterocolitis: fungal sepsis

From 1979 to 1986, 82 infants underwent surgical treatment for necrotizing enterocolitis (NEC), with 36 deaths. The records of 30 of the 36 infants who died were available for review. Fungal colonization and sepsis, the sites of infection, and timing of diagnosis and therapy were determined. Sixteen of 30 (53%) neonates had no evidence of fungus. Six (20%) were colonized with Candida species. Eight (27%) had fungal sepsis, with two of these eight found only at necropsy. Positive fungal blood cultures were a late finding. In only four of the six patients with positive blood cultures were the results known in time to initiate treatment with amphotericin B. Two of these four babies received less than 2 days of amphotericin B treatment prior to death. Fungal sepsis is a significant lethal factor in the surgical mortality of NEC. Vigorous efforts at earlier diagnosis are mandatory.     

Bilateral ischemic optic neuropathy and retinal vascular occlusions associated with lymphoma and sepsis. Clinicopathologic correlation

The authors report the clinicopathologic correlation of a patient with non-Hodgkin's mixed-cell lymphoma who had impairment of the circulation of the optic nerve and retina in both eyes. The results of histopathologic examination showed that the pial septa of the optic nerves were infiltrated by lymphoma and that there was extensive infarction of the orbital portions of both optic nerves and occlusion of both central retinal arteries and the right central retinal vein by thrombi with bacteria. The infiltration of the optic nerves seemed to be resistant to therapy.     

Induction of MHC class II expression in recipient tissues caused by allograft rejection

MHC class II antigens (DR) are not commonly expressed on parenchymal cells of kidney and liver except when they are allografts undergoing rejection. The objective of this study was to determine whether allograft rejection can also induce DR upregulation in parenchymal cells of autologous recipient organs. Dogs had unilateral renal autografts to facilitate kidney sampling. All kidneys were tubular cell DR-negative. After 8-14 days each dog received a tubular cell DR-negative allograft. Tubular cell DR became positive in both allograft and autograft simultaneously, its onset and intensity correlating with blast cell infiltration and rejection in the allograft. Blast cells were first detected in the autograft after allograft nephrectomy, and then disappeared as autograft tubular cell DR diminished over the next 6-8 days. This was reproduced on repeat allografting. In 2 untreated dogs hepatocytes became positive on day 4, with no hepatic blast infiltrate. Four other dogs received cyclosporine immunosuppression. Allograft and autograft tubular cell DR, and hepatocyte DR, increased in all dogs, but were delayed while on CsA until onset of rejection despite transient earlier allograft blast infiltration. Downregulation in autograft and liver occurred together after allograft nephrectomy. An interferon-like substance appeared in plasma after allografting in association with the DR changes in native kidney and liver. Renal allorejection therefore induces upregulation of parenchymal DR expression in autologous liver and kidney of the recipient. It is probably mediated by an interferon-like substance derived from cells infiltrating the allograft. The effect is modified by CsA.     

Cerebral blood flow changes in normal aging: Spect measurements

Global and regional cerebral blood flow (CBF) were evaluated with single photon emission computerized tomography (SPECT) utilizing both ¹³³Xenon (¹³³Xe) (47 subjects, 47–82 years old) and ⁹⁹Tc-hexamethylpropyleneamine oxime (⁹⁹Tc-HMPAO) (27 subjects, 47–80 years old). The ¹³³Xe results showed: among total subjects, no age-related decline in global CBF, but a significant regional decline in the occipital lobe (p < 0.05); among men, significant age-related declines in global, frontal, temporal, occipital and right hemisphere CBF (all p < 0.05); among women, no age-related decline in global or regional CBF. The ⁹⁹Tc-HMPAO results showed no age-related decline in either global or regional perfusion among total subjects, men or women. These results suggest that age-related global and regional (including frontal lobe) CBF declines do not occur in healthy control subjects after the age of 45 years. However, gender differences in age-related CBF changes warrant further study.