Reductions in lymphocyte subpopulations after repeated exposure to 1.5 ppm nitrogen dioxide.

In this investigation the effects of repeated exposure to 1.5 ppm NO2 on immune competent cells in bronchoalveolar lavage (BAL) fluid was studied. Special attention was focused on effects on lymphocyte subpopulations. Eight healthy subjects were exposed to 1.5 ppm NO2 every second day on six occasions. Bronchoalveolar lavage fluid was collected at least three weeks before the exposure series as reference and 24 hours after the last exposure. The results obtained were analysed using a non-parametric test for paired observations, with each subject as his own control. Significant reductions were found in the total number and percentage of T cytotoxic-suppressor cells in BAL fluid; this caused an increase in the ratio of T helper-inducer: cytotoxic-suppressor cells. The total number of natural killer cells in the BAL fluid was also reduced. The numbers of all other cell types were unchanged after exposure. No reduction of phagocytosis of opsonised yeast particles by alveolar macrophages in vitro was detected. It is concluded that repeated short term exposures to 1.5 ppm NO2, a moderate occupational concentration, induces significant effects on immune competent bronchoalveolar lymphocytes. This indicates that previous findings of changes in the lymphoid immune system induced by NO2 in animals may well be applicable to humans.     

Adenosine induced chest pain--a comparison between intracoronary bolus injection and steady state infusion.

OBJECTIVE: Adenosine may induce chest pain in at least two ways, either by direct stimulation of sensory afferents before actual ischaemia occurs or secondary to ischaemia. The aim was to study if the mechanism of pain induction may depend on the method of adenosine administration. METHODS: Increasing doses of adenosine were given to seven male patients with ischaemic heart disease referred for coronary angiography: first as a bolus intracoronary injection (2.5-50 mumol), second as a 1 ml.min-1 steady state infusion (0.01-20 mumol.min-1) and third as an intravenous steady state infusion (0.076-0.76 mumol.kg-1 x min-1). Pain, rate-pressure product, coronary sinus blood flow, and ECG were monitored. Lactate was analysed in coronary sinus and arterial blood. RESULTS: After intracoronary bolus injection there were no signs of myocardial ischaemia, whereas during intracoronary steady state infusion, and in spite of a lower, but definite, degree of pain, 5/7 patients showed myocardial lactate production and three patients showed ST depression. During the intravenous steady state infusion 6/6 patients showed ST depression. CONCLUSIONS: These findings suggest that when using adenosine for studies on the mechanisms of chest pain in patients with ischaemic heart disease it is preferable to use an intracoronary bolus injection technique rather than a steady state infusion, as the risk of inducing ischaemia with the latter model cannot be ignored.     

Development of tyrosine hydroxylase-, dopamine- and dopamine β-hydroxylase-immunoreactive neurons in a teleost, the three-spined stickleback

The development of catecholaminergic neuronal systems in the brain of a teleost, the three-spined stickleback, was studied through embryonic to early larval stages by immunocytochemistry using specific antibodies against dopamine, tyrosine hydroxylase and dopamine β-hydroxylase. By analysing the spatiotemporal patterns of development for the catecholaminergic nuclei, possible homologies with nuclei in amniote brains have been identified.

The noradrenergic neurons in the isthmus region of the rostral rhombencephalon originate in the same manner as the A4–A7 + subcoeruleus group in mammals. Their developmental characteristics show the largest similarities with the subcoeruleus group of birds and mammals, although some features are shared with developing A6 (locus coeruleus) neurons.

Catecholaminergic neurons never appear during development in the ventral mesencephalon of the three-spined stickleback. A group of large dopaminergic neurons that accompany the cerebrospinal fluid (CSF)-contacting neurons follows the border between the hypothalamus and the ventral thalamus into the caudal hypothalamus, where they are continuous with the dopaminergic neurons in the posterior tuberculum. They are thus topologically comparable with the dopaminergic neurons of the zona incerta in mammals.

The dopaminergic CSF-contacting neurons that line the median, lateral and posterior recesses of the third ventricle do not contain tyrosine hydroxylase-immunoreactivity at any developmental stage. This indicates that they take up and accumulate exogenous dopamine or -dihydroxyphenylalanine, and do not synthesize dopamine from tyrosine at any developmental stage. Tyrosine hydroxylase-immunoreactive neurons appear in the pineal organ on the day of hatching (120 h post-fertilization). They were still observed in 240-h-old larvae, but are absent in the pineal organ of adult sticklebacks.

The initial appearance and subsequent differentiation of catecholaminergic neurons in the stickle-back embryo follow essentially the same spatial and temporal pattern as in amphibian, avian and mammalian embryos. This observation supports the hypothesis that morphologically, topologically and chemically similar monoaminergic neurons in different vertebrate classes are homologous.     

Bone mineral density in patients with prostatic cancer treated with orchidectomy and with estrogens

Bone mineral density (BMD) and bone mineral content (BMC) were measured in the femoral neck area, trochanteric area and Wards triangle, and in the distal radius of the left forearm before and after 1 year of endocrine treatment in 27 patients with prostatic cancer. Eleven of the patients were treated with orchidectomy and 16 with combined oral and intramuscular estrogens. The patients were free from metastases during the entire observation period. In the orchidectomized patients, BMD and BMC of the distal radius decreased significantly following treatment, whereas no changes were observed in the estrogen-treated patients. These preliminary results demonstrate that estrogens may protect bone in male subjects also and may merit further investigations on larger groups of patients.     

Bacterial colonization and infection in an intensive care unit

One hundred and one patients, nursed in an intensive care unit for at least 24h, were monitored for bacterial colonization and infection. The infection rates were similar to those in other reports. Patients were not generally colonized with common environmental strains in the unit. Bacterial dissemination between patients was uncommon. No gentamicin resistant gram negative or Staphylococcus aureus strains were observed, nor methicillin resistant Staphylococcus aureus strains. the hypothesis that these favourable conditions are partly related to the excellent isolation and barrier nursing facilities in the unit cannot be fully substantiated.     

Clinical significance of autoantibodies against neutrophil cytoplasmic components in patients with renal disease

The diagnostic significance of anticytoplasmic autoantibodies (ANCA) was studied in 71 renal patients. The ANCA test was positive in 67% of patients with Wegener's granulomatosis (WG), in 35% of those with a simultaneous renal and respiratory tract disease but not diagnosed as WG and in 22% of patients with a renal disease associated with unspecific collagenosis/vasculitis. Among WG patients ANCA positivity clearly correlated with the presence of active renal disease. Interestingly, both ANCA-positive and -negative patients were encountered in the group with acute renal failure and acute extracapillary glomerulonephritis associated with diffuse pulmonary infiltrates. The diagnostic and clinical significance of the ANCA test in these cases remains for the present obscure. In the majority of the ANCA-positive renal patients with respiratory tract abnormalities, the antibodies showed diffuse cytoplasmic staining and were mostly of the IgG class, of both IgG and IgM classes in some cases and of IgG, IgM and IgA classes in 1 patient. In patients with unspecific vasculitis/collagenosis the level of ANCA was rather low, and the distribution of different isotypes resembled that of patients with respiratory symptoms. A certain isotype of ANCA or staining pattern did not mark out any clinicopathologic subgroup among the patients. Our findings indicate that the clinical picture of ANCA-positive patients varies considerably and the ANCA test may not be as specific a marker of WG as previously suggested.     

Multiple sclerosis: myelin basic protein induced mRNA expression of proinflammatory cytokines in mononuclear cells is suppressed by interferon-β 1b in vitro

Beta-interferon (IFN-β) is a promising treatment in multiple sclerosis (MS), reducing the exacerbation rate and MRI lesion burden, as well as the disease progression in relapsing-remitting MS. IFN-β was originally defined by its antiviral effects, but the interest has recently been focused on its immunomodulatory properties. Myelin basic protein (MBP) is one of several autoantigens considered to be the target for autoaggressive immune responses, which eventually might lead to the development of MS. To study in-vitro effects of IFN-β1b on MBP induced cytokine expression, mRNA for the Th1 cytokines IFN-γ and TNF-α, the Th2 related IL-4 and IL-6, the cytolytic perforin and the immune response downregulating TGF-β was measured with in situ hybridization after culture of blood mononuclear cells (MNC) in the presence and absence of MBP. Numbers of cells expressing IFN-γ, TNF-α, perforin and IL-4 mRNA were significantly suppressed after culture with 10 U/ml IFN-β1b. No such effect was seen on MBP induced IL-6 or TGF-β mRNA expression. These observations suggest that one of the major effects of IFN-β1b is the induction of a shift in the cytokine mRNA profile towards a more immunosuppressive pattern. In parallel in vitro tests, the control substance dexametasone (40 μg/ml) reduced the numbers of cells expressing mRNA for all cytokines under study with the exception of TGF-β, to an extent equal to or even more pronounced than IFN-β1b.