Growth rate characteristics of acoustic neuromas associated with neurofibromatosis type 2

Neurofibromatosis type 2 (NF2) is a dominantly inherited disorder characterized by the occurrence of bilateral acoustic neuromas (ANs and other central nervous system tumors. Magnetic resonance images and audiologic data on 22 patients with NF2 who underwent multiple studies at the National Institutes of Health between 1983 and 1993 were reviewed to determine the growth characteristics of ANs in these patients. The average growth rate of ANs in NF2 patients was 0.30 cm3 per year and was significantly higher in older patients (0.75 cm3 per year) than in younger ones (0.12 cm3 per year). Larger ANs were more commonly found in patients with concomitant spinal tumors or meningiomas. NF2 patients with spinal tumors but not meningiomas demonstrated faster growth rates than patients without additional tumor burden. The data from this study suggest that older patients or patients with associated spinal tumors have faster growing ANs and therefore should be followed closely and treated aggressively.     

Germ-line mutations in the neurofibromatosis 2 gene: correlations with disease severity and retinal abnormalities

Neurofibromatosis 2 (NF2) features bilateral vestibular schwannomas, other benign neural tumors, and cataracts. Patients in some families develop many tumors at an early age and have rapid clinical progression, whereas in other families, patients may not have symptoms until much later and vestibular schwannomas may be the only tumors. The NF2 gene has been cloned from chromosome 22q; most identified germ-line mutations result in a truncated protein and severe NF2. To look for additional mutations and clinical correlations, we used SSCP analysis to screen DNA from 32 unrelated patients. We identified 20 different mutations in 21 patients (66%): 10 nonsense mutations, 2 frameshifts, 7 splice-site mutations, and 1 large in-frame deletion. Clinical information on 47 patients from the 21 families included ages at onset and at diagnosis, numbers of meningiomas, spinal and skin tumors, and presence of cataracts and retinal abnormalities. We compared clinical findings in patients with nonsense or frameshift mutations to those with splice-site mutations. When each patient was considered as an independent random event, the two groups differed (P < or = .05) for nearly every variable. Patients with nonsense or frameshift mutations were younger at onset and at diagnosis and had a higher frequency and mean number of tumors, supporting the correlation between nonsense and frameshift mutations and severe NF2. When each family was considered as an independent random event, statistically significant differences between the two groups were observed only for mean ages at onset and at diagnosis. A larger data set is needed to resolve these discrepancies. We observed retinal hamartomas and/or epiretinal membranes in nine patients from five families with four different nonsense mutations. This finding, which may represent a new genotype-phenotype correlation, merits further study.     

Chronic lymphatic leukemia. Peroral cladribine as primary treatment

Ten patients with newly diagnosed B-chronic lymphocytic leukaemia were treated with cladribin orally for five days every four weeks with a median of four series. This is the first reported clinical study where a purine analogue is administered orally. The tumour reducing effect was fast. Eight out of 10 patients responded with a partial or clinical complete remission. Two of these were in molecular biological complete remission. With an observation time of 22 months we have seen no serious side effects so far. A randomized study (including a long term follow up) between chlorambucil, fludarabin and cladribin is needed to clarify the future role of cladribin in B-CLL treatment.     

Psychogenic stress: theory, experiment, practice

Experiments on animals (rodents, beasts, primates) and observation in man have ascertained that psychogenic stress is the most important defensive state of living organisms, which is constantly involved in order to maintain their interaction with external psychogenic factors. Three types of stress should be distinguished, these include normostress, hypostress, and hyperstress. Normostress has definite limits within which optimal responses, which are typical for an individual are realized. Hyperstress develops as a defensive response to extremely strong (extraordinary) stimuli. Hypostress can be observed in the retarded development of self-regulation mechanisms. All three types of stress are provided by a fundamental property of living organisms--the self-regulation mechanism, which realizes the keeping back of normostress constancy, or return of hyper- and hypostress to the normostress status. And only if an extreme deficit of self-regulation mechanisms takes place, hyper(hypo)stress could become a condition for the development of pathology.     

Stability of fumonisins in thermally processed corn products

Little is known about the stability of fumonisins in corn-based foods during heating. This study investigated the effects of canning, baking, and roasting (dry heating) processes on the stability of fumonisins in artificially contaminated and naturally contaminated corn-based foods. All samples were analyzed for fumonisin levels by both a commercial enzyme-linked immunosorbent assay (ELISA) and a high-performance liquid chromatographic (HPLC) method. Canned whole-kernel corn showed a significant (P < or = 0.05) decrease in fumonisins by both ELISA (15%) and HPLC (11%) analyses. Canned cream-style corn and baked corn bread showed significant (P < or = 0.05) decreases in fumonisin levels at an average rate of 9% and 48%, respectively, as analyzed by ELISA. Corn-muffin mix artificially contaminated with 5 micrograms of fumonisin B1 (FB1) per g and naturally contaminated corn-muffin mix showed no significant (P < or = 0.05) losses of fumonisins upon baking. Roasting cornmeal samples artificially contaminated with 5 micrograms of FB1 per g and naturally contaminated cornmeal samples at 218 degrees C for 15 min resulted in almost complete loss of fumonisins.     

Visualizing the dynamics of T cell activation: intracellular adhesion molecule 1 migrates rapidly to the T cell/B cell interface and acts to sustain calcium levels

T cell recognition typically involves both the engagement of a specific T cell receptor with a peptide/major histocompatibility complex (MHC) and a number of accessory interactions. One of the most important interactions is between the integrin lymphocyte function-associated antigen 1 (LFA-1) on the T cell and intracellular adhesion molecule 1 (ICAM-1) on an antigen-presenting cell. By using fluorescence video microscopy and an ICAM-1 fused to a green fluorescent protein, we find that the elevation of intracellular calcium in the T cell that is characteristic of activation is followed almost immediately by the rapid accumulation of ICAM-1 on a B cell at a tight interface between the two cells. This increased density of ICAM-1 correlates with the sustained elevation of intracellular calcium in the T cell, known to be critical for activation. The use of peptide/MHC complexes and ICAM-1 on a supported lipid bilayer to stimulate T cells also indicates a major role for ICAM-1/LFA-1 in T cell activation but, surprisingly, not for adhesion, as even in the absence of ICAM-1 the morphological changes and adhesive characteristics of an activated T cell are seen in this system. We suggest that T cell antigen receptor-mediated recognition of a very small number of MHC/peptide complexes could trigger LFA-1/ICAM-1 clustering and avidity regulation, thus amplifying and stabilizing the production of second messengers.     

Structure functional expression and spatial distribution of a cloned cDNA encoding a rat 5-HT1D-like receptor

Using polymerase chain reaction (PCR) a complementary DNA (cDNA) encoding a 5-hydroxytryptamine (5-HT) receptor was isolated from rat forebrain. The amplified cDNA specifies an open reading frame of 374 amino acids comprising seven putative transmembrane regions. Expression of the cloned cDNA in human embryonic kidney cells (HEK 293) was used to establish the pharmacological profile of the encoded receptor polypeptide. Membranes containing the cloned receptor showed high affinity binding of [3H]-5-HT. Competition binding experiments with a variety of serotonin receptor ligands displayed a rank order of affinities corresponding to a 5-HT1D subtype: 5-CT > 5-HT = metergoline > CGS 12066 > methysergide > sumatriptan > mianserin = (-)alpha-Me-5-HT = yohimbine > 8-OH-DPAT > or = rauwolscine > spiperone > DOI > propranolol > or = 2-Me-5-HT > or = ICS 205930. Ketanserin and ritanserin displaced [3H]-5-HT-binding in a biphasic manner. In situ hybridization revealed highest expression of the corresponding mRNA in the pyramidal layer of the olfactory tubercle and the nucleus caudatus and accumbens.     

A prospective randomized comparison of epidural infusion of fentanyl and intravenous administration of morphine by patient-controlled analgesia after radical retropubic prostatectomy

In a prospective, randomized study, continuous infusion of epidural fentanyl citrate (group E) was compared with patient-controlled intravenously administered morphine sulfate (group P) for analgesia in 66 men after radical retropubic prostatectomy. Although both methods provided satisfactory analgesia, the mean comfort level scores were lower (that is, greater comfort) in group E than in group P at all observation times. The difference in mean resting comfort level scores between groups E and P was statistically significant (P < or = 0.05) at 9 of the 11 observation times. In addition, significant differences in comfort level scores were noted at 8 of the 11 observation times during deep breathing, 5 of 11 during coughing, and 3 of 9 during ambulation. Maximal and minimal comfort level scores recorded by each patient during the course of the study were significantly lower (that is, less pain) in group E than in group P for all four categories of activity. The percentage of patients who reported no pain was significantly higher in group E than in group P at 9 of 11 observation times during resting and 5 of 11 observation times during deep breathing. No significant differences were noted in side effect profiles or duration of hospital stay. In summary, when two effective methods of analgesia used after radical retropubic prostatectomy were compared prospectively, patients who received epidural infusion of fentanyl were more comfortable than those with patient-controlled intravenous administration of morphine, as evidenced by lower mean, maximal, and minimal comfort level scores and a greater proportion of patients with complete relief of pain.     

Separation of bacterial capsular and lipopolysaccharides by preparative electrophoresis

Preparative gel electrophoresis was used to separate and purify extracellular, capsular and lipopolysaccharides (EPSs, CPSs, and LPSs, respectively) from crude bacterial extracts. The procedure effectively separates CPS from LPSs. In addition discreet size ranges of these various polysaccharides can be isolated. The 'rough' (R-type), 'smooth' (S-type), and 'semi-smooth' LPSs were separated from one another. In addition different size classes of 'semi-smooth', or S-type LPS, can be separated. This procedure was demonstrated for diverse bacterial species, including the soil bacteria Rhizobium fredii, and the enteric bacterial species, Salmonella enteritidis and Proteus mirabilis. In the latter case, it was also possible to separate capsular polysaccharide from its lipid-bound form.