Reactive plasmacytoses are expansions of plasmablasts retaining the capacity to differentiate into plasma cells.

Circulating plasma cells in 10 cases of reactive plasmacytosis had a shared phenotype with early plasma cell (CD19(+) CD38(+) CD138(+) CD40(+) CD45(+) CD11a+ CD49e- CD56(-)). In most cases, a minor subpopulation of CD28(+) plasma cells was also detected. Reactive plasma cells were highly proliferative, suggesting the presence of circulating progenitors (plasmablasts). After CD138(+) plasma cell removal, highly proliferative CD138(-) plasmablasts differentiated into CD138(+) plasma cells within a few days. This differentiation, which was associated with increased CD38 and decreased HLA-DR expression, was further confirmed by a large increase in intracellular Ig content (associated with Ig secretion) and was concomitant with extensive secretion of interleukin-6 (IL-6). The addition of neutralizing anti-IL-6 and anti-CD126 (IL-6 receptor) monoclonal antibodies totally prevented Ig secretion and cell differentiation by inducing apoptosis of plasmablasts, which indicates that IL-6 is an essential survival factor for plasmablasts. This report provides the first characterization of normal plasmablasts and shows that their phenotype is not exactly that of multiple myeloma cells.     

Influence of the speed of spheronization on the physical properties and dissolution availability of theophylline minigranules prepared by extrusion-spheronization]

From the minigranules of the theophylline-based that prepared by extrusion-spheronization, the authors have envisaged the study of one of the parameters of operation (spheronizer speed) on the physical properties and lyoavailability of the active ingredient. It emerges that there is a clear influence of that parameters on the particle size distribution, the hardness, the friability, the density and the lyoavailability.     

Myeloma cells upregulate interleukin-6 secretion in osteoblastic cells through cell-to-cell contact but downregulate osteocalcin

Previous studies have shown that bone marrow, especially the bone microenvironment, may play an important role in the pathogenesis of multiple myeloma (MM). To elucidate the relationship between myeloma cells and bone cells, mainly osteoblasts, we have established a coculture system between two interleukin-6 (IL-6)-dependent myeloma cell lines, XG1 and XG6, and the osteosarcoma cell lines Saos-2 and MG63. Both osteosarcoma cell lines have retained major functions of normal osteoblasts; principally, the capacity to produce hematopoietic growth factors (including IL-6) and osteocalcin, a noncollagenic protein essential in the bone formation process. Because IL-6 is a critical growth factor in MM, we have examined the IL-6 osteoblastic cell production in our coculture system. XG1 cells strongly upregulate IL-6 production by MG63 and Saos-2 cells. Of major interest, the triggering of IL-6 is totally dependent on the physical contact between myeloma cells and osteoblastic cells, contact that is partly mediated by CD44, CD56, and fibronectin interactions. Osteocalcin production by MG63 and Saos-2 cells has previously been shown to be dependent on 1,25- (OH)2D3. We demonstrate that XG1 and XG6 cells reduced the amount of osteocalcin in MG63 coculture cell supernatants, a reduction that is partly mediated by a soluble factor and by cell-to-cell contact. Notably, whereas one of the myeloma cell lines, XG6, has lost its capacity to stimulate IL-6 production by osteoblastic cell lines, both XG1 and XG6 cell lines remain able to reduce the osteocalcin amount, indicating that IL-6 and osteocalcin levels are regulated by two different pathways. In conclusion, these data strongly support the concept that the bone microenvironment is directly modified by contact with myeloma cells and are consistent with the characteristics observed in vivo in patients with MM patients, ie, abnormally high IL-6 and low osteocalcin levels, respectively.     

Histologic evidence of an abnormal bone remodeling in B-cell malignancies other than multiple myeloma

In a prospective study of the quantitative bone changes induced by B-cell cancers other than multiple myeloma (MM), but including chronic lymphocytic leukemia (CLL; n = 8), hairy cell leukemia (HCL; n = 3), and Waldenstr?m disease (WD; n = 7), an abnormal bone remodeling close to malignant cells was found in 80% of the patients. This was observed more frequently in cases of diffuse, but not nodular, bone marrow involvement by tumor cells. More particularly, excessive bone resorption (a major feature of MM) associated with a normal to low bone formation (i.e., uncoupling bone disease) was the most frequent feature and in the same range of that observed in overt MM. However, as opposed to MM, this bone resorption was characteristically mediated by small mononucleated osteoclasts (i.e., microresorption). The same phenomena of abnormal bone remodeling, the uncoupling process, excessive bone resorption, and above all microresorption were confirmed by the detailed bone study of five cases of B-cell cancers other than MM presenting lytic bone lesions and hypercalcemia. The current findings are important for clarifying the biology of these B-cell malignant diseases, and also could be of diagnostic and prognostic value.     

Peripheral neuropathy during treatment with ornidazole

The case is reported of an 18 year old patient who developed a peripheral neuropathy after being given 1.5 g ornidazole daily for 6 days and 2 g daily for 16 days (total dose: 41 g). Bilateral radial paralysis was noted clinically, whilst electrical investigations showed diffuse motor and sensitive anomalies. Three months after the drug had been stopped, all symptoms and signs had disappeared. The pathogenesis of this complication is discussed. The part played by ornidazole is suggested but cannot be proved because of the multiple disorders presented by the patient.     

Infantile spinal muscular atrophy

The authors report 100 cases with prolonged spinal muscular atrophy (SMA) and survival beyond 4 years old. There were 46 boys and 54 girls. 23 of them had histories with an autosomal recessive form of inheritance. One case had a dominant form. The unity of cases described as Werdnig Hoffman disease [SMA I, SMA II (Childhood), ans SMA III (Kugelberg Welander)] is supported and our cases fell in three groups according to their ambulatory capabilities: never acquired, lost, or retained. 71 cases have never walked: the onset of symptoms was noted at an average age of 6.4 months +/- 3; the average age at the last examination was 16 years (4-39). Death occurred in 6 cases. Loss of walking occurred in 24 cases: the onset of symptoms was noted at an average age of 17.4 months +/- 14.2. 5 cases were still ambulatory: the onset of symptoms was noted at an average age of 2.4 years +/- 2.8. For these last 29 cases the average age at the last examination was 20 years (4-38); death occurred in two cases. The weakness was symmetrical and proximal. The period of worsening varied but, frequently, patients with a later onset of symptoms had a longer period of deterioration. Tongue fasciculations were present in all cases who never walked. Facial and masseter weakness occurred in 3 cases. Oesophagus dyskinesia and distension of the stomach due to brain stem lesions occurred in many cases. This brain stem damage was responsible of 2 sudden deaths (8-30 years). Premature puberty occurred in 14 cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Heterogeneity of protein hormones in radioimmunoassay]

Radioimmunoassay measures antigenic determinants of hormonal molecules in the plasma and tissues. These estimations carried out after fractionation in biological fluids, have revealed several immunological forms of the same hormone. These immunoreactive forms may be added to already well known elements of hormonal heterogeneity: formation of aggregate, polymerisation, links to transport proteins, microheterogeneity by silent mutation. The main problem is in the relationship of the various immunoreactive forms to the same hormonal sequence. The similar immunoreactive forms of high molecular weight (big hormone) usually have low biological activity and suggest the presence of prohormone; the suggestion of prohormonal nature depends on the chronology of the incorporation of labelled leucine and enzymatic transformation of prohormone with low biological into active hormone. The forms with high molecular weight and similar immunological activity may be of another nature. Thus, it has been shown that the biosynthetic nature of a compound such as big big insulin in the rat is doubtful owing to the absence of specific incorporation of labelled leucine into the immunoprecipitate of this fraction. The significance of low molecular weight forms is still little known. There may be breakdown products, biologically active products or biosynthetic products. An example of these forms is supplied by the existence of an alpha sub-unit of gonadotrophin present in the plasma of menopausal women. The interest of analytical methods by radio-receptor, stimulation of cyclase activity in the identification of biological activity of immunoreactive forms, is discussed in relation to immunological forms of enteroglucagon. An unusual aspect of the evolutive and adaptative character of hormonal heterogeneity is given by the gastro-intestinal hormones: secretin, vasoactive intestinal polypeptide and enteroglucagon, have similar structure and mode of action; however, the existence of a specific receptor is a sign of their functional differentiation at molecular level.