Polyphosphoinositide synthesis in human neutrophils. Effects of a low metabolic energy state

Phosphatidylinositol (PtdIns) synthesis and polyphosphoinositide (PPI) formation were measured as the incorporation of [32P]orthophosphate ([32P]Pi) or [3H]inositol into non-stimulated intact human neutrophil membrane phospholipids. The rate of PtdIns "de novo" synthesis appeared to be a slow mechanism when compared to the rapid incorporation of [32P]Pi into PPIs. Of the "de novo" synthesized [3H]PtdIns, 70% was further phosphorylated to PPI. Nevertheless, this PPI pool represented less than 0.01% of the total nmols of PPIs formed evaluated as [32P]Pi labeling, indicating that PPI formation mainly involves a no "de novo" synthesized phosphatidylinositol pool. When evaluated at short incubation times, oscillations in the formation of PPIs were detected. A rapid phase was characterized after 30 s of incubation with [32P]Pi Phosphorylation levels returned to an equilibrium state within a minute, and the second phase peaked at 5 min., returning to equilibrium at 15 min. The fluctuant kinetics though not the equilibrium level of PPI formation, could be abolished by neomycin. On the other hand, a selective inhibition of the rapid phase of PPI synthesis occurred in the presence of the tyrosine kinase inhibitor genistein. When the incorporations of [gamma-32P]-adenosine triphosphate (ATP) or [32P]Pi into human neutrophil particulate fraction membranes were evaluated, PPIs synthesis showed fluctuations independently of the precursor used. Noticeably, [32P]from [32P]Pi was incorporated more efficiently into PPIs than that from [gamma-32P]ATP, when evaluated in parallel using equal specific activities for both radiolabeled precursors and under non-ATP synthesizing conditions. Moreover, the incorporation of [32P]Pi into particulate fraction PPIs was not abolished by high concentrations of non-radiolabeled ATP, and metabolically inhibited PMNs showed high rates of PPI synthesis. These data suggest that PPI formation is not necessarily a futile cycle in PMNs.     

A nucleolus-associated coiled body

One or two healthy structures frequently have been observed attached to nucleoli in facial motor neurons of the golden hamster. These round-to-oval structures, called "coiled bodies", were seen at 15, 19, and 24 days postnatal and in the adult, both in normal neurons and in chromatolytic neurons which had been axotomized 4 days previously. With one exception, the coiled bodies were seen to be attached via fibrillar material to the nucleolar periphery. Although the numbers of coiled bodies may be altered during neuronal maturation and as a result of axon section, the bodies revealed no structural alterations that could be attributed to developmental age or to experimental trauma.     

Silicon and aluminium interactions in haemodialysis patients

BACKGROUND: Aluminium toxicity in dialysis patients is well described. Aluminium has a close chemical affinity with silicon. Silicon may have a role in protection against aluminium toxicity. METHODS: We measured serum aluminium and silicon levels from haemodialysis patients from four different centres. RESULTS: Though no relationship was seen across all centres combined, in one centre there was a reciprocal relationship in patients on home haemodialysis (who did not require reverse osmosis). Median (range) aluminium levels were higher, 2.2 (0.4-9.6) micromol/l when serum silicon was less than 150 micromol/l, and lower, 1.1 (0.2-2.8) micromol/l when serum silicon levels were greater than 150 micromol/l (P = 0.03). CONCLUSIONS: In patients treated by haemodialysis without reverse osmosis high serum silicon concentrations were associated with lower serum aluminium concentrations than those with low serum silicon. Further work needs to confirm a preventative role for silicon in the accumulation and subsequent toxicity of aluminium in dialysis patients.     

Dynamic course of neurological syndromes in very young children with the history of intrauterine growth retardation

90 infants with intrauterine growth retardation (IGR) and 100 normal infants (control group) were followed up from 5 days till 3 years of life. In IGR infants there was a more frequent combination of several neurologic syndromes, an early manifestation of motor disorders (from the very moment of birth), a delay of neuro-psychic development (during the first year of life), a tendency to development of moderate hydrocephalus by the age of 6 months. Autonomic-visceral disorders in them were mostly characterized by the symptoms of abaissement, but not of irritation.     

Maximum-tolerated dose, toxicity, and efficacy of (131)I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma

PURPOSE: Lym-1, a monoclonal antibody that preferentially targets malignant lymphocytes, has induced remissions in patients with non-Hodgkin's lymphoma (NHL) when labeled with iodine 131 ((131)I). Based on the strategy of fractionating the total dose, this study was designed to define the maximum-tolerated dose (MTD) and efficacy of the first two, of a maximum of four, doses of (131)I-Lym-1 given 4 weeks apart. Additionally, toxicity and radiation dosimetry were assessed. MATERIALS AND METHODS: Twenty patients with advanced NHL entered the study a total of 21 times. Thirteen (62%) of the 21 entries had diffuse large-cell histologies. All patients had disease resistant to standard therapy and had received a mean of four chemotherapy regimens. (131)I-Lym-1 was given after Lym-1 and (131)I was escalated in cohorts of patients from 40 to 100 mCi (1.5 to 3.7 GBq)/m2 body surface area. RESULTS: Mean radiation dose to the bone marrow from body and blood (131)I was 0.34 (range, 0. 1 6 to 0.63) rad/mCi (0.09 mGy/MBq; range, 0.04 to 0.17 mGy/ MBq). Dose-limiting toxicity was grade 3 to 4 thrombocytopenia with an MTD of 100 mCi/m2 (3.7 GBq/m2) for each of the first two doses of (131)I-Lym-1 given 4 weeks apart. Nonhematologic toxicities did not exceed grade 2 except for one instance of grade 3 hypotension. Ten (71 %) of 14 entries who received at least two doses of (131)I-Lym-1 therapy and 11 (52%) of 21 total entries responded. Seven of the responses were complete, with a mean duration of 14 months. All three entries in the 100 mCi/m2 (3.7 MBq/m2) cohort had complete remissions (CRs). All responders had at least a partial remission (PR) after the first therapy dose of (131)I-Lym-1. CONCLUSION: (131)I-Lym-1 induced durable remissions in patients with NHL resistant to chemotherapy and was associated with acceptable toxicity. The nonmyeloablative MTD for each of the first two doses of (131)I-Lym-1 was 100 mCi/m2 (total, 200 mCi/m2) (3.7 GBq/m2; total, 7.4 GBq/m2).     

Choices: biomedical ethics and women''s health. Ethical issues and dilemmas

Distribution of markers of local cell-mediated immunity was examined in oral tumors exhibiting different histological stages of differentiation. Using a RT-PCR-based semiquantitative technique we determined levels of Langerhans cells, CD4- and CD8-positive T-cells, macrophages/NK cells, beta2-microglobulin and IFN-gamma mRNAs from tissue biopsies. A positive correlation was found between levels of these immunological markers and the tumor differentiation stage. Since tumor differentiation may correlate with the prognosis and response to various treatment modalities, our results may be useful clinically.     

The value of palpation as basis for decision on lymph node excision

The purpose of the study was to evaluate palpation of the regional lymph nodes in control examinations of patients with malignant disease. A retrospective review of the medical records of 188 cases in which the patients had had an extirpation of the regional lymph nodes was performed. We have compared the preoperative findings through palpation with the histological diagnosis. The patients were grouped according to the region in which the lymph node removal had been done. The specificity of palpation when the histological diagnosis was malignant was (with 95% confidence limits), in the axilla 0.65 (0.54-0.75), in the inguinal region 0.86 (0.75-0.94) on the neck 0.83 (0.52-0.98) and in the suprahyoid region 0.58 (0.28-0.85). In conclusion, palpation of regional lymph nodes is not a sufficient control examination in the estimation of the course of malignant disease. Supplementary examination methods are recommended.