Identification of a novel antigenic structure of the human receptor for interleukin-6 involved in the interaction with the glycoprotein 130 chain

PURPOSE: To evaluate the diagnostic accuracy of positron emission tomography (PET) with administration of 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) relative to that of magnetic resonance (MR) imaging and/or computed tomography (CT) in recurrent head and neck cancers. MATERIALS AND METHODS: Twelve adult patients (mean age, 63 years) with previously treated head and neck cancers and clinical suspicion of recurrence underwent FDG PET and MR imaging and/or CT. All images were blindly and independently interpreted without histopathologic findings (obtained within 1 week of imaging). The level of confidence in image interpretation was graded by using a five-point rating system (0 = definitely no recurrence to 4 = definite recurrence). RESULTS: Recurrence was confirmed in eight patients. With a rating of 4 as a positive finding, FDG PET yielded a sensitivity and specificity of 88% (seven of eight) and 100% (four of four), respectively; MR imaging and/or CT, 25% (two of eight) and 75% (three of four), respectively. Receiver-operating characteristic analysis showed significantly better diagnostic accuracy with FDG PET than with MR imaging and/or CT (area under curve = 0.96 vs 0.55, P < .03). CONCLUSION: These data indicate that PET metabolic imaging, as compared with anatomic methods, has improved diagnostic accuracy for recurrent head and neck cancer.     

Identification of novel simple sequence length polymorphisms (SSLPs) in mouse by interspersed repetitive element (IRE)-PCR

Interspersed repetitive element (IRE)-PCR is a useful method for identification of novel human or mouse sequence tagged sites (STSs) from contigs of genomic clones. We describe the use of IRE-PCR with mouse B1 repetitive element primers to generate novel, PCR amplifiable, simple sequence length polymorphisms (SSLPs) from yeast artificial chromosome (YAC) clones containing regions of mouse chromosomes 13 and 14. Forty-two IRE-PCR products were cloned and sequenced from eight YACs. Of these, 29 clones contained multiple simple sequence repeat units. PCR analysis with primers derived from unique sequences flanking the simple sequence repeat units in seven clones showed all to be polymorphic between various mouse strains. This novel approach to SSLP identification represents an efficient method for saturating a genomic interval with polymorphic genetic markers that may expedite the positional cloning of genes for traits and diseases.     

Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis

The antitumor effect and mechanisms activated by murine IL-12 and IL-18, cytokines that induce IFN-gamma production, were studied using engineered SCK murine mammary carcinoma cells. In syngeneic A/J mice, SCK cells expressing mIL-12 or mIL-18 were less tumorigenic and formed tumors more slowly than control cells. Neither SCK.12 nor SCK.18 cells protected significantly against tumorigenesis by distant SCK cells. However, inoculation of the two cell types together synergistically protected 70% of mice from concurrently injected distant SCK cells and 30% of mice from SCK cells established 3 d earlier. Antibody neutralization studies revealed that the antitumor effects of secreted mIL-12 and mIL-18 required IFN-gamma. Interestingly, half the survivors of SCK.12 and/or SCK.18 cells developed protective immunity suggesting that anti-SCK immunity is unlikely to be responsible for protection. Instead, angiogenesis inhibition, assayed by Matrigel implants, appeared to be a property of both SCK.12 and SCK.18 cells and the two cell types together produced significantly greater systemic inhibition of angiogenesis. This suggests that inhibition of tumor angiogenesis is an important part of the systemic antitumor effect produced by mIL-12 and mIL-18.     

Transdural spinal cord herniation: imaging and clinical spectra

OBJECTIVE: Many diseases induce asymmetric delays in the visual pathway, resulting in a spontaneous Pulfrich phenomenon (PP). The PP is a visual stereoillusion that may cause difficulties in persons when traveling in cars, crossing the road, or playing ball games. The authors developed and tested a simple new bedside procedure to detect PP. DESIGN: A case series. PARTICIPANTS: Disease simulation in 2 normal subjects and 18 patients with optic neuritis (ON) was examined. Ninety normal subjects were studied to determine normal range of PP. INTERVENTION: The new test, called swinging pen test (SPT), is performed by oscillating a pen by hand. The SPT was compared to a gold standard, a mechanical pendulum (MP). MAIN OUTCOME MEASURES: The authors measured simulated PP in two normal subjects and PP in 18 patients with ON and 90 normal control subjects. The Pearson product-moment correlation (r) and the Spearman rank correlation (rs) between SPT and MP were calculated. RESULTS: The magnitudes of simulated PP determined with the SPT and the MP correlated well (r = 0.92, P < 0.005, and r = 0.96, P < 0.001). Correlation also was good in patients with ON (rs = 0.90, P < 0.05). The positive predictive value of the SPT was 100%, and the negative predictive value was 92%. The PP was absent in all control subjects testing with either pendulum. The normal range for PP varied from -1.40 to 1.52 msec. For the SPT, the intraobserver variability coefficient was 8.2%, and the interobserver variability coefficient was 10.5%. CONCLUSIONS: The authors believe that SPT will be of value to clinicians on bedside evaluation of motion stereopsis dysfunctions. The normal range of PP was approximately +/- -1.5 msec (approximately +/- -1.5 cm), corresponding to a 0.3-log unit neutral density filter).     

Treatment of aplastic anaemia with antilymphocyte globulin and cyclosporin

Improved survival of patients with aplastic anaemia (AA) has been reported over the last 20 years with immunosuppressive (IS) therapy using antilymphocyte globulin (ALG), and more recently cyclosporin (CSA). The antibody specificities of ALG have now been more clearly defined and are not only T cell directed but also include activities against B cells, NK cells and monocytes. Consequently, the effectiveness of ALG in AA may involve several different mechanisms, and may also help to explain the delayed response that occurs in AA. CSA increases the response rate to ALG in the first 3-6 months, but does not result in improved survival compared with ALG alone. Better supportive care has undoubtedly contributed to the improved survival of patients with time. Almost half the patients who do not respond to a first course of ALG can achieve a later response with a second course of ALG. Relapse occurs in 30% of patients, but up to 50% will respond again with a second course of ALG. Evaluation of the expression of (1) phosphatidylinositol-glycan (PIG)-anchored proteins on haemopoietic cells and (2) gamma-IFN in bone marrow mononuclear cells, may help to predict which patients are more likely to respond to IS therapy. Long term follow up of patients is required to assess the predictive value of X-inactivation DNA studies and PIG-protein expression for later clonal evolution.     

Cardiac single-photon emission tomography with a 90 degrees dual-head system

Dual-head single-photon emission tomography (SPET) systems which permit a 90 degrees orientation of the heads provide a twofold increase in sensitivity for 180 degrees SPET compared with single-head systems. Since such systems have additional mechanical and electrical alignment and stability requirements, clinical equivalency for myocardial perfusion SPET must be demonstrated. Accordingly, we studied 26 subjects who underwent exercise thallium scintigraphy consecutively with both single-head and dual-head systems. Image acquisition was similar, except that the dual-head study took one-half the time. Image reconstruction was identical. Images were interpreted in a blinded fashion, and rated for technical quality. All 26 studies were equivalently interpreted for the presence or absence of perfusion defects. Fourteen of the studies were judged to be technically equivalent; seven were judged to be slightly better with the single-head system; three were judged to be slightly better with the dual-head system; and two were judged to be definitely better with the dual-head system. We conclude that dual-head 90 degrees systems provide equivalent clinical performance in half the acquisition time.     

Extended reproductive roles of the fruitless gene in Drosophila melanogaster revealed by behavioral analysis of new fru mutants

The fruitless mutants fru3 and fru4 were assessed for sex-specific reproductive-behavioral phenotypes and compared to the previously reported fru mutants. Among the several behavioral anomalies exhibited by males expressing these relatively new mutations, some are unique. fru3 and fru4 males are less stimulated to court females than fru1 and fru2. No courtship pulse song is generated by either fru3 or fru4 males, even though they perform brief wing extensions. fru3 and fru4 males display significantly less chaining behavior than do fru1 males. The hierarchy of courtship responses by fru males directed toward females vs. males, when presented with both sexes simultaneously, is that fru1 males perform vigorous and indiscriminant courtship directed at either sex; fru4 males are similarly indiscriminant, but courtship levels were lower than fru1; fru2 males prefer females; fru3 males show a courtship bias toward males. fru3 and fru4 males essentially lack the Muscle of Lawrence (MOL). On several reproductive criteria, there was no difference between fru-variant females and fru+. The increases in phenotypic severity measured for the new mutants are discussed in the context of the emerging molecular genetics of fru and with regard to the gene's position within the sex-determination pathway.     

Evolution of the local calcium content around irradiated beta-tricalcium phosphate ceramic implants: in vivo study in the rabbit

To evaluate whether dissolved calcium from tricalcium phosphate implants contributes to osseous wound healing in bone defects, the authors used nuclear radioactivated materials. Six months after irradiation, the calcium was still radioactive. Samples of the material were prepared and placed in rabbit condyles for 1, 3 and 9 months. Over time the condyles were retrieved and treated for histology or radiocounting. Measurements of the radioactivity of the slices and histomorphometry of the implants and surrounding tissues were performed. The authors observed that the radioactivity decreased regularly. Connective tissue had penetrated the pores and totally invaded the implants, first at the periphery of the implants, then inside the pores. Comparison of the results of radioactivity and histomorphometry suggest that part of the calcium from the implants was re-used specifically in the new osseous tissue.     

The link between drug use and heart valve disease

We report MRI and angiographic findings of an unusual giant arachnoid granulation in the left sigmoid sinus in a boy with headache. Its signal intensity was lower than that of cerebral cortex on T1-weighted images and higher on T2 weighting, mimicking dural sinus thrombosis.