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Biomedical subjects

M Togni

Publications and source records attributed to M Togni.

8 recordsLinked to original sources

Heterozygous defect in HIV-1 coreceptor CCR5 and chemokine production.

CC chemokine receptor 5 (CCR5) is a cell entry cofactor for macrophage-tropic isolates of human immunodeficiency virus 1 (HIV-1). An inactive CCR5 allele with a 32-nucleotide deletion (CCR5Delta32) has been described that confers resistance to HIV-1 infection in homozygotes and slows the rate of progression to AIDS in heterozygotes. We found the allele CCR5Delta32 to be not rare in 399 Swiss blood donors with a frequency of 0.080. To assess the influence of defective CCR5 on production of its ligands we determined the capacity to produce the chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and RANTES in comparison with the production of the CXC chemokine IL-8 which does not bind to CCR5. Production of chemokines was determined during endotoxin stimulation of whole-blood samples ex vivo. Both, basal and LPS-induced chemokine production in 32 blood donors heterozygous for CCR5Delta32 were not significantly different when compared with 55 blood donors who were homozygous for the wild type CCR5 allele.

Alleles↗

Neural and endogenous catecholamines in the bone marrow. Circadian association of norepinephrine with hematopoiesis?

Members of our research team have recently reported that adrenergic agents may affect hematopoiesis via alpha1-adrenoceptors present on bone marrow B cell precursors. In this paper we demonstrate that murine bone marrow contains a substantial amount of catecholamines. Norepinephrine (NE) and dopamine (DA) exhibited a daily rhythmicity, with peak values observed during the night. The rhythm was disrupted by chemical sympathectomy, whereas epinephrine (E) showed no rhythmicity or sensitivity to 6-hydroxydopamine. High and low values of NE and DA were associated with high and low values of their metabolites, which indicated a rhythmic catecholamine release. NE, but not DA or E, was positively associated with the proportion of cells in the G2/M and S phases of the cell cycle. Moreover, NE and DA were found in both short-term and long-term bone marrow cultures as well as in human or murine B lymphoid cell lines. These findings indicate that endogenous catecholamines in the bone marrow have both neural and cellular origins. The neural input shows a daily rhythm and may be implicated in the regulation of hematopoiesis.

Animals↗

[Reversible posterior leukoencephalopathy: significance in everyday clinical practice].

Reversible posterior leukoencephalopathy (PLE) is a newly recognized syndrome with characteristic radiologic findings. The clinical picture resembles that of hypertensive encephalopathy. PLE is caused by uncontrolled hypertension as well as other neurotoxic conditions. We report on 3 patients with this syndrome. One patient also had transient hydrocephalus which may have been caused by PLE. Clinicians must be aware of this syndrome as its recognition obviates unnecessary diagnostic procedures. PLE is reversible by lowering elevated blood pressure and treating neurotoxic conditions such as uremia.

Adult↗

Norepinephrine protects mice from acute lethal doses of carboplatin.

We demonstrated in previous studies that adrenergic agents may affect hematopoiesis via high- and low-affinity alpha1-adrenoceptors present on bone marrow (BM) cells [1-3]. Here we show that norepinephrine administration in mice rescued hematopoiesis from the toxic effect of the non-cell cycle specific chemotherapeutic agent, carboplatin. Protection of granulocyte/macrophage colony-forming units (GM-CFUs) was already apparent only a few hours after carboplatin and norepinephrine administration. On day 3, hematopoietic rescue was reflected by higher leukocyte and platelet counts. At its most effective dose (3 mg/kg, subcutaneously injected), norepinephrine protected 77% of the mice previously injected intravenously with 200 mg/kg of carboplatin (LD 100: 170 mg/kg). Simultaneous administration of the alpha1-adrenoceptor antagonist prazosin reduced the percentage of surviving mice to 30%, indicating that alpha1-adrenoceptors mediated most of the norepinephrine-induced hematopoietic rescue. Consistently, prazosin administration also reduced blood counts and GM-CFUs. In vitro, norepinephrine (1 microM) rescued GM-CFUs in BM cells, although this effect was counteracted by low concentrations (0.1-10 nM) of prazosin. Our findings indicate a previously undescribed novel mechanism of hematopoietic regulation and may find application in preventing the myeloablative effect of anticancer treatments.

Adrenergic alpha-Antagonists↗

Pancreatic calcifications in patients with chronic pancreatitis. A sign of long-lasting or severe disease?

Pancreatic calcifications are particularly frequent in patients with severe pancreatic insufficiency and long-lasting chronic pancreatitis. To clarify whether calcifications point to a more severe form of the disease, irrespective of its duration, we have retrospectively analyzed patients with chronic pancreatitis submitted to the secretin-cerulein test in our center over a six-year period. Out of 120 patients, calcifications were found in 55. Higher alcohol intake and longer duration of the disease were found in patients with calcifications, compared with patients without calcifications (p less than 0.001). In both groups, lipase and chymotrypsin were more severely impaired than bicarbonate; a greater reduction of pancreatic exocrine function was found in patients with calcifications, compared to those without (p less than 0.001, Mann-Whitney U-test). When the patients were classified according to the duration of the disease or the severity of exocrine function impairment, higher percentages of patients with calcifications were found in the classes with more advanced disease. A log-linear analysis showed that the prevalence of calcifications was associated with pancreatic function impairment, even within the same class of duration of the disease. It is likely that calcifications mark more severe forms of chronic pancreatitis, even in the early phases of the disease.

Adolescent↗

Rapid diagnosis of pancreatic cancer by combination of ultrasonography and serum tumour markers CA 19-9 and CA 50.

Non-invasive tests such as ultrasonography (US) and serum CA 19-9 or CA 50 present substantial sensitivity, but are not devoid of false-negative results in the diagnosis of pancreatic cancer. The patient sample in this study comprised 58 patients, 51 with adenocarcinoma, 4 with cystadenocarcinoma, 2 with islet-cell carcinoma and 1 with anaplastic carcinoma. All the patients underwent US examination with evaluation of visible tumour volume by means of the sphere or ellipsoid rotation formula. Serum CA 19-9 was measured in all cases, and CA 50 in 50. Pancreatic tumours were diagnosed by US in 47/58 patients [sensitivity (S) = 81.03%] and ductal carcinomas in 46/55 (S = 83.6%). Abnormal CA 19-9 values were found in 48/58 subjects (S = 82.7%) and in 47/55 ductal carcinomas (S = 85.4%). CA 50 showed abnormal values in 39 of the 50 tumours assessed (S = 78%) and in 38/47 ductal carcinomas (S = 80.8%). Combined use of the tests considerably improves these sensitivities. It is concluded that US results can be improved when combined with the two antigen assays. The poor correlation between tumour mass and serum antigen levels is compensated for by the US performance. The combination of US plus CA 19-9 and CA 50 provides a very good tool for the rapid non-invasive diagnosis of pancreatic cancer.

Adenocarcinoma↗