Magnetization transfer imaging in progressive multifocal leukoencephalopathy

We report a patient with biopsy-proven progressive multifocal leukoencephalopathy (PML) who was serially imaged with MRI and magnetization transfer imaging. The magnetization transfer ratio (MTR) was profoundly and significantly diminished when compared with normal control subjects. The pattern of MTR was distinct from that of MS and periventricular ischemic white matter disease. Magnetization transfer imaging techniques may aid in the differential diagnosis of PML.     

Apolipoprotein E-associated risk for Alzheimer's disease in the African-American population is genotype dependent

As a part of our ongoing study on Alzheimer's disease (AD) in elderly African Americans, we obtained clinical assessment and apolipoprotein E (ApoE) genotype data on 288 individuals (including 60 with AD). The ApoE epsilon4 allele frequency was significantly increased in AD patients compared with controls. The age-adjusted odds ratio (OR) for AD in epsilon4 homozygotes was 4.83 (95% confidence interval [CI], 1.71-13.64) compared with the epsilon3/epsilon3 genotype, but the OR for AD with the epsilon3/epsilon4 genotype did not reach significance (1.20; 95% CI, 0.58-2.45). These findings suggest that the association between ApoE epsilon4 and AD is weaker in African Americans than in whites.     

Detection of terminal deoxynucleotidyl transferase (TdT) in nonhematopoietic small round cell tumors of children

In the differential diagnosis of small round cell tumors (SRCTs), terminal deoxynucleotidyl transferase (TdT) is often used as a marker for lymphoblastic lymphomas and leukemias. However, the specificity of TdT using the avidin-biotin-immunoperoxidase (ABC) method is not well documented. To address this issue, we stained paraffin-embedded biopsy specimens of 64 cases of childhood SRCTs using the ABC method with anti-TdT. For any TdT-positive tumors, an additional antibody panel for lymphoid markers was applied. Two patterns of TdT positivity were observed: (1) tumor specific, consisting of strong to moderate nuclear staining, and (2) scattered positive lymphoid cells, usually in a perivascular location and expressing T-cell markers. Analysis showed that 7 of 10 medulloblastomas stained with TdT in a tumor-specific pattern (4 cases moderately to strongly positive in 75-100% of tumor cells, 3 cases weakly to moderately positive in 25-50% of cells). Also, 1 of 19 rhabdomyosarcomas and 1 of 8 Ewing's sarcomas showed moderate to strong tumor-specific TdT staining in 100 and 10% of cells, respectively. Scattered TdT-positive lymphoid cells were observed in 27% of these 64 SRCTs. These findings emphasize that TdT positivity should not be relied upon exclusively for making a diagnosis of lymphoblastic leukemia or lymphoma or ruling out other SRCTs.     

Rotational vertebral artery occlusion: a mechanism of vertebrobasilar insufficiency

OBJECTIVE: Symptomatic dynamic changes in blood flow secondary to vertebral artery compression with rotational head motion are evaluated in a series of patients as a cause for posterior circulation transient ischemic attacks. These cases are classic examples of rotational vertebral artery occlusion and allow for the discussion of the anatomic basis, angiographic features, and treatment options. ILLUSTRATIVE CASES: In our series, symptoms of vertebrobasilar insufficiency were reproducible with rotational head movement. Compression of the vertebral artery was demonstrated angiographically. The correct site of occlusion of the vertebral artery was apparent only by dynamic angiography with progressive head rotation. All of the patients presented in the illustrative cases had occlusion at the C2 level; however, one patient had been previously misdiagnosed and another had an additional site of occlusion. The anatomic course of the vertebral artery is described in addition to the sites of rotational occlusion. CONCLUSION: Rotational vertebral occlusion is an important cause of vertebrobasilar symptoms, which may lead to permanent neurological deficit if left undiagnosed. Dynamic angiography is the established method of diagnosis. Great care must be taken to avoid misdiagnosing the site of occlusion or missing a second occlusive site. For this reason, it is crucial to have a thorough understanding of the anatomic course of the vertebral artery and the muscular and tendinous insertions, which may cause rotational occlusion. The decision for treatment must be based on the site of occlusion as well as the assessment of the patient as a surgical candidate. A review of the literature reveals that surgical treatment is effective and must be considered to avoid further morbidity.     

Differential recruitment of leukocyte populations and alteration of airway hyperreactivity by C-C family chemokines in allergic airway inflammation

Allergic airway inflammation is characterized by peribronchial leukocyte accumulation within the airway. Subsequent tissue damage leading to airway hyperreactivity is a result of activation of multiple leukocyte populations. Using an established model of allergic airway inflammation induced by intratracheal challenge with parasite (Schistosoma mansoni) egg Ag in presensitized mice, we have examined differential leukocyte recruitment. These studies have identified key chemokines involved in the accumulation of specific subsets of cells and the induction of airway hyperreactivity. In this study we have examined three C-C family chemokines, MCP-1, MIP-1alpha, and RANTES, which promote mononuclear cell- and eosinophil-specific recruitment to the airway. The in vivo neutralization of either MIP-1alpha or RANTES, but not MCP-1, significantly reduced the intensity of the eosinophil recruitment to the lung and airway during the allergic airway response by >50 and >60%, respectively. In contrast, neutralization of MCP-1 significantly reduced total leukocyte migration (>50% reduction), whereas neutralization of RANTES and MIP-1alpha had no significant affect on the overall leukocyte migration. Further examination of the effect of MCP-1 depletion indicated that both CD4+ and CD8+ lymphocyte subsets were decreased. Depletion of MCP-1 significantly reduced the airway hyperreactivity to near control levels, whereas depletion of MIP-1alpha or RANTES did not affect the intensity of airway hyperreactivity. These data indicate that multiple C-C chemokines are involved in the recruitment of particular leukocyte populations and that neutralization of MCP-1, but not RANTES or MIP-1alpha, significantly reduced airway hyperreactivity.     

Faster recovery in central than in peripheral auditory system following a reversible cochlear deafferentation

Research has shown that various perinatal conditions increase the likelihood of offending behavior; however, results have been mixed, but interactions among perinatal risk factors in predicting offending behavior have been neglected. The purpose was to examine the interaction of maternal cigarette smoking during pregnancy and 1-min. Apgar scores at birth in predicting individuals' later offending behavior. The longitudinal data set was taken from the Philadelphia portion of the Collaborative Perinatal Project and consisted of 832 inner-city, African-American youths. A logistic regression analysis indicated that the combined effect of maternal cigarette smoking and low Apgar scores had a significant influence in predicting offending behavior, whereas the independent effects of the component variables did not.     

Citation for the Distinguished Physician Award of the Endocrine Society to Dr. John P. Bilezikian

OBJECTIVE: To elucidate the molecular mechanism of smoking cessation and its relationship to body weight gain, the effects of smoking on the serum levels of leptin were studied in Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The serum levels of leptin after an overnight fast in 37 adult male Japanese patients with type 2 diabetes (17 smokers and 20 nonsmokers) were assayed using radioimmunoassay. In addition, the serum leptin levels in four nondiabetic smokers were measured before and 2 weeks after quitting smoking. RESULTS: Smokers and nonsmokers did not differ in age, BMI, or levels of blood glucose and fasting insulin but did differ in HDL cholesterol levels (1.07 +/- 0.18 vs. 1.32 +/- 0.24 mmol/l for smokers and nonsmokers, respectively, P = 0.002). The mean serum leptin level of smokers did not differ from that of nonsmokers (3.8 +/- 1.9 vs. 3.8 +/- 1.6 ng/ml). The leptin level correlated with the fasting insulin level and BMI (r = 0.55 and 0.56, P < 0.001 and 0.001, respectively). The leptin levels in four heavy smokers showed no change after the subjects quit smoking (3.3 +/- 1.0 vs. 3.8 +/- 1.8 ng/ml, before and after quitting, respectively). CONCLUSIONS: Because smoking did not affect the leptin levels, the effects of quitting smoking on the fuel metabolism appear to be due to some other factors.     

Relationship between the ability of sunscreens containing 2-ethylhexyl-4''-methoxycinnamate to protect against UVR-induced inflammation, depletion of epidermal Langerhans (Ia+) cells and suppression of alloactivating capacity of murine skin in vivo

Phalloidin was shown to increase the ATPase activity and Ca2+ sensitivity of both bovine cardiac and rabbit psoas myofibrils when assayed in a solution containing 50 mM KCl, 100 mM MOPS (pH 7.0), 2 mM MgCl2, 1 mM ATP, 2 mM EGTA, and varying concentrations of Ca2+ (temperature 21-22 degrees C). The phalloidin effect in cardiac myofibrils developed over a time course of several minutes in the presence of 50 microM phalloidin. Relative increase of ATPase activity was maximal at pCa 8 and decreased with decrease in pCa. In cardiac myofibrils the increase was about 70% at pCa 8 and 20% at pCa 4 following 20-30 min pre-incubation with 2 microM or 50 microM phalloidin. The effect persisted after excess phalloidin was washed out. The increase in Ca2+ sensitivity was approximately 0.15 pCa units. For skeletal myofibrils treated with 2 microM phalloidin all changes were considerably less than those seen with cardiac myofibrils and the changes were even less when the myofibrils were exposed to 50 microM phalloidin. These results show that when specifically bound to actin, phalloidin can change the kinetic parameters of the cross-bridge cycle and may also alter the Ca2+ sensitivity of the contractile system. The effects of phalloidin seem to vary with muscle type.