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- Diab, Asim, et al.
(författare)
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Neutralization of macrophage inflammatory protein 2 (MIP-2) and MIP-1α attenuates neutrophil recruitment in the central nervous system during experimental bacterial meningitis
- 1999
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 67:5, s. 2590-2601
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Tidskriftsartikel (refereegranskat)abstract
- Chemokines are low-molecular-weight chemotactic cytokines that have been shown to play a central role in the perivascular transmigration and accumulation of specific subsets of leukocytes at sites of tissue damage. Using in situ hybridization (ISH), we investigated the mRNA induction of macrophage inflammatory protein 2 (MIP-2), MIP-1α, monocyte chemoattractant protein 1 (MCP-1), and RANTES. Challenge of infant rats’ brains with Haemophilus influenzae type b intraperitoneally resulted in the time-dependent expression of MIP-2, MIP-1α, MCP-1, and RANTES, which was maximal 24 to 48 h postinoculation. Immunohistochemistry showed significant increases in neutrophils and macrophages infiltrating the meninges, the ventricular system, and the periventricular area. The kinetics of MIP-2, MIP-1α, MCP-1, and RANTES mRNA expression paralleled those of the recruitment of inflammatory cells and disease severity. Administration of anti-MIP-2 or anti-MIP-1α antibodies (Abs) resulted in significant reduction of neutrophils. Administration of anti-MCP-1 Abs significantly decreased macrophage infiltration. Combined studies of ISH and immunohistochemistry showed that MIP-2- and MIP-1α-positive cells were neutrophils and macrophages. MCP-1-positive cells were neutrophils, macrophages, and astrocytes. Expression of RANTES was localized predominantly to resident astrocytes and microglia. The present study indicates that blocking of MIP-2 or MIP-1α bioactivity in vivo results in decreased neutrophil influx. These data are also the first demonstration that the C-C chemokine MIP-1α is involved in neutrophil recruitment in vivo.
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| 2. |
- Hu, Jie
(författare)
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Non-invasive assessment of dynamic properties in human arteries : with special reference to gestation and diabetes
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The important role played by the intrinsic properties of central arteries in cardiovascular physiology and pathology has been increasingly recognised. Several circulatory disorders are associated with increased arterial stiffness. To better understand the arterial functions in diabetes and their relevance to pregnancy, we have employed recent improvements in technology for non-invasive investigation of the dynamic functions both in large arteries and in microvasculature. Our main purposes were to enhance the application of these techniques for vascular measurements, and to clarify the large-arterial wall function in mother and fetus in normal pregnancy and in pregnancy complicated with diabetes, and to investigate macro- and microvascular properties in non-pregnant women with a history of gestational diabetes (GDM), as well as in children and adolescents with insulin-dependent diabetes mellitus (IDDM). Study population and methods: Totally 341 subjects participated in this series of investigations, including (1) fetuses and women in uncomplicated or diabetic pregnancy; (2) non- pregnant women with a GDM history and their age-matched controls; and (3) children and adolescents with IDDM and their age- and gender-matched controls. To evaluate the mechanical properties of the descending aorta and carotid artery, an ultrasonic, phase-locked, zero-crossing echo tracking system was employed. The microcirculatory reactivities in the skin of the foot and hand were assessed using a laser Doppler technique. Results: The pulse wave velocity (PWV) in the fetal aorta increased from the 28th to the 36th gestational week, and then remained constant during the last month of uncomplicated pregnancy; however, a few days before spontaneous parturition it declined significantly. The fetal aortic PWV depended on fetal behavioural states as well as on the presence or absence of fetal breathing movements. Reduced maternal aortic stiffness was found in the first trimester of uncomplicated pregnancy; however, this change, regarded as a cardioprotective adaptation, did not appear in pregnant women complicated with IDDM. Two-to-four years after a pregnancy complicated with GDM, apparently healthy women had stiffened carotid arteries and impaired acetylcholine-induced vasodilatation in the skin microvasculature. An age-related increase in aortic stiffness started already around ten years of age, soon after puberty boys having a stiffer aorta than girls. In children and adolescents with IDDM and without clinical evidence of cardiovascular complications, the aorta was stiffer than in their age- and gender-matched non- diabetic controls; but only in diabetic girls after puberty. In addition, microcirculatory reactivities were disturbed in children and adolescents with IDDM, but the degree of aortic stiffness and the microvascular reactivity of the foot skin were not statistically interrelated. Conclusions: Evaluation of vascular dynamic properties provides assessment of patho-physiological functions in the vessels of fetuses and their mothers, as well as in subjects with IDDM or at high risk of developing NIDDM. The macro- as well as the microvascular disturbances found in young persons with uncomplicated IDDM, and in women with previous GDM history, might be early markers of cardiovascular complications to their diabetes. The present non- invasive methods are suitable for large-scale studies to detect vascular lesions in a high-risk population.
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