The development of lateral-line receptors in Eigenmannia (Teleostei, Gymnotiformes). II. The electroreceptive lateral-line system

Weakly electric fish of the genus Eigenmannia were induced to spawn in conditions simulating the tropical rainy season. The skin of embryos of different ages was prepared for histological examination, and whole animals were examined by various histological methods and scanning electron microscopy. It was found that the electrosensory system develops after the first mechanoreceptive lines have formed. The tuberous and ampullary organs initially form adjacent to the lines of the lateral-line system. The tuberous organs develop at a rate 5 times higher than that of the ampullary organs. The rate of development for both classes of electroreceptors is 4 times higher on the head than on the trunk. The first tuberous organs develop on the head at day 7 and on the trunk at day 8. They increase in number and size during the growth of the fish. The ampullary organs begin to form on the head and on the most rostral part of the trunk at day 8. They are deeply sunk into the corium and have the same number of receptor cells as in adults. There are both ampullary and tuberous organs within fields of receptors that are innervated by a single nerve branch.     

Molecular interactions of Leishmania promastigote surface protease with human alpha 2-macroglobulin

The interaction of Leishmania promastigote surface protease (PSP) with the plasmatic protease inhibitor alpha 2-macroglobulin (alpha 2M) was investigated. In plasma, solubilized PSP forms covalent complexes only with alpha 2M, at the exclusion of other protease inhibitors. The formation of complexes is accompanied by the proteolytic cleavage of the alpha 2M subunit and by the transition from the 'slow' to the 'fast' form of alpha 2M. The proteolytic activity of solubilized PSP on azocasein is inhibited by alpha 2M. In contrast, we found no evidence for a specific interaction of alpha 2M with the surface of promastigotes and PSP proteolytic activity on intact cells was not inhibited by alpha 2M.     

Cell surface antigen CD5 is a marker for activated human B cells

A minor subset of B cells which in vivo express the surface antigen CD5, has attracted much attention because of its involvement in autoimmune responses. On the basis of observations showing self-renewal capacity of such cells in mice and also the absence of a substantial change of CD5 phenotype during B cell activation in vitro, the CD5+ B cells are now generally considered to represent a separate cell lineage. In the present study, CD5- B cells were isolated by cell sorter and then stimulated in vitro with mutagenized EL4 thymoma cells in the presence of T cell supernatant. About 70% of the B cells were CD5+ after 3 days. Thus, the CD5 antigen behaves as a B cell activation marker. In our system we found that the frequency of rheumatoid factor-producing B cells was on average three times higher in CD5+ than in CD5- B cells isolated ex vivo from human peripheral blood. Most likely this reflects frequent activation of such autoreactive B cells in vivo.     

The treatment of hypertension in very old persons: Benefits and limitations

The treatment of arterial hypertension is a key strategy for the prevention of stroke and heart failure even in very old hypertensive patients. However, it is a challenging public health task given the sheer number of patients, the complexity, duration and cost of treatment and safety issues. To avoid overtreatment, it is important to confirm the diagnosis with 24-hour ambulatory blood pressure (BP) monitoring or BP monitoring at home. A systolic BP of 150 mmHg (135–140 mmHg with out-of-office measures) is an acceptable cut-off value both for the diagnosis of hypertension and as a target for treatment in most patients more than 80 years old. Avoiding “going too low” not only at the initiation of therapy, but also during follow-up, is important for treatment safety. Treatment should be initiated and followed up in a shared decision-making process, taking the patients’ preferences into account. These strategies will help to ensure treatment adequacy and safety. Conversely, the fear of drug-induced orthostatic hypotension should in itself only rarely be a reason not to treat.     

Major lower limb amputations in the elderly observed over ten years: the role of diabetes and peripheral arterial disease

BACKGROUND: Major amputation is a dreaded event with high mortality and morbidity. However, few studies have investigated the epidemiology of amputation in the elderly over time, in the face of evolving management and prevention efforts. METHODS: We undertook a retrospective study to determine the incidence rate, etiology and prognosis of major lower limb amputations (transtibial or higher) in elderly patients (> 65 years). Cases were identified over a 10-year period in the Geneva (Switzerland) area, where all amputations are performed in a single center and reliable demographic data are available. RESULTS: The rate of amputation varied from 1.8 to 11.4/10000 patients/year, increasing with age and male gender. Diabetes was present in 48% patients, and conferred a 10 times higher risk of amputation. Severe peripheral arterial disease (PAD) was present in > 94% patients. The prognosis remains poor, 47% patients had died after two years and only 53% patients could be equipped with a prosthetic limb. Over 10 years we found a progressive increase in age at amputation; this encouraging increase was mostly accounted for by diabetic patients (> 6 months per year). CONCLUSIONS: The rate of amputation observed among elderly patients was low. Neither the rate nor the prognosis improved over the decade studied. However, the age at amputation increased by > 6 months/year, particularly in diabetic amputees, suggesting that current management successfully delays amputation. Amputations were almost exclusively performed for severe PAD. Further reduction in the rate of amputation will require progress in the prevention and management of PAD.     

Tissue-type plasminogen activator (t-PA) is stored in Weibel-Palade bodies in human endothelial cells both in vitro and in vivo

Vascular endothelial cells are thought to be the main source of plasma tissue-type plasminogen activator (t-PA) and von Willebrand factor (VWF). Previous studies have suggested that both t-PA and VWF are acutely released in response to the same stimuli, both in cultured endothelial cells and in vivo. However, the subcellular storage compartment in endothelial cells has not been definitively established. We tested the hypothesis that t-PA is localized in Weibel-Palade (WP) bodies, the specialized endothelial storage granules for VWF. In cultured human umbilical vein endothelial cells (HUVECs), t-PA was expressed in a minority of cells and found in WP bodies by immunofluorescence. After up-regulation of t-PA synthesis either by vascular endothelial growth factor (VEGF) and retinoic acid or by sodium butyrate, there was a large increase in t-PA-positive cells. t-PA was exclusively located to WP bodies, an observation confirmed by immunoelectron microscopy. Incubation with histamine, forskolin, and epinephrine induced the rapid, coordinate release of both t-PA and VWF, consistent with a single storage compartment. In native human skeletal muscle, t-PA was expressed in endothelial cells from arterioles and venules, along with VWF. The 2 proteins were found to be colocalized in WP bodies by immunoelectron microscopy. These data indicate that t-PA and VWF are colocalized in WP bodies, both in HUVECs and in vivo. Release of both t-PA and VWF from the same storage pool likely accounts for the coordinate increase in the plasma level of the 2 proteins in response to numerous stimuli, such as physical activity, beta-adrenergic agents, and 1-deamino-8d-arginine vasopressin (DDAVP) among others.     

Effect of glycemic control on the overnight dexamethasone suppression test in patients with diabetes mellitus.

Because many of the clinical features associated with Cushing's syndrome are frequently found in patients with diabetes mellitus, diabetic patients are often evaluated for Cushing's syndrome. The initial test for Cushing's syndrome is the 1 mg overnight dexamethasone suppression test (DST), but its value as a screening test in diabetic subjects, especially those with poor glycemic control, has been questioned. To address this issue, an overnight DST was administered to 100 subjects with diabetes. Only 7 patients failed to suppress their plasma cortisol to less than 140 nmol/L (5.0 micrograms/dL), achieving a specificity of 93%. There was no relation between acute glycemic control (as measured by the mean of 4 serum glucose values obtained before receiving dexamethasone) or chronic glycemic control (as measured by glycohemoglobin) and false positive responses to the 1 mg overnight DST. The mean of the measures of acute glycemic control of the 7 subjects who had false positive results, 14.4 +/- 2.8 mmol/L, was not significantly different than that of the 93 subjects with normal responses, 13.2 +/- 3.3 mmol/L. Similarly, the mean glycohemoglobin of the subjects with false positive results, 12.8 +/- 2.4%, was not significantly different than that of the subjects with normal responses, 12.9 +/- 2.5%. There was no correlation between plasma cortisol after dexamethasone and glycohemoglobin (r = 0.05), and only a weak correlation with the mean serum glucose (r = 0.21). We conclude that the 1 mg overnight DST is a valid screening test for Cushing's syndrome in patients with diabetes, regardless of glycemic control.     

Inhibitors of interleukin 1 activity in synovial fluids and in cultured synovial fluid mononuclear cells.

Measurement of interleukin 1 (IL-1) in synovial fluids (SF) yielded variable results and implied the presence of an inhibitory activity. As peripheral blood monocytes produce an IL-1 receptor antagonist (IL-1ra), we investigated whether SF mononuclear cells (SFMC) also secreted such inhibitory activity. MC isolated from inflammatory SF produced, in addition to variable levels of IL-1, a specific IL-1 inhibitor of approximately 23 kDa which blocked both IL-1 biological activity and binding to its receptor. Western blot, using a polyclonal antibody to rhIL-1ra, indicated that SFMC secreted material that shared immunological crossreactivity with the cloned IL-1ra. IL-1 inhibitory activity was also detected in SF but not formally demonstrated to be related to IL-1ra. In conclusion, SFMC could produce IL-1ra and an imbalance between IL-1 and its specific antagonist may be relevant to the severity of joint destruction.