A meta-analysis of non-Hodgkin's lymphoma among farmers in the central United States

A meta-analysis of studies examining the association between non-Hodgkin's lymphoma (NHL) and employment as a farmer in the central United States was performed to verify the observation by Blair et al. [1993] that this group is at excess risk of NHL. Six studies were selected for the meta-analysis, and the estimator of relative risk calculated was 1.34 (95% confidence interval (CI) = 1.17, 1.55). Exposures associated with NHL and associated with agricultural commodities frequently produced in the central United States are infectious microorganisms and pesticides. Examination of the production patterns of the farms in this region did not reveal a single specific risk factor consistently found on all farms; however, past production patterns suggest that exposure to either infectious microorganisms or pesticides might be a risk factor for NHL in this group of farmers.     

A major gene affecting age-related hearing loss in C57BL/6J mice

A major gene responsible for age-related hearing loss (AHL) in C57BL/6J mice was mapped by analyses of a (C57BL/6J x CAST/Ei) x C57BL/6J backcross. AHL, as measured by elevated auditory-evoked brainstem response (ABR) thresholds, segregated among backcross mice as expected for a recessive, primarily single-gene trait. Both qualitative and quantitative linkage analyses gave the same genetic map position for the AHL gene (Ahl on chromosome 10, near D10Mit5. Marker assisted selection was then used to produce congenic lines of C57BL/6J that contain different CAST-derived segments of chromosome 10. ABR test results and cochlear histopathology of aged progenitors of these congenic lines are presented. Ahl is the first gene causing late-onset, non-syndromic hearing loss that has been reported in the mouse.     

Social phobia: long-term treatment outcome and prediction of response--a moclobemide study

In this open, prospective, structured, naturalistic study of the efficacy of long-term treatment in social phobia 93 consecutive outpatients suffering from severe generalized or circumscribed social phobia (median Liebowitz Social Anxiety Scale score 83) and a high degree of concomitant psychiatric disease were administered treatment with moclobemide (712 +/- 75 mg/day at steady state). Fifty-nine patients who responded (Clinical Global Impression for Change: very much/much improved) completed 2 years of treatment. Patients then entered a drug-free period of at least 1 month during which 88% of the patients deteriorated. In a further 2-year treatment period with moclobemide those patients who had deteriorated became responders again. Symptoms recurred in a substantial number of the patients at the end of the study when the dose was reduced and then discontinued. Post-study follow up at 6-24 months after study completion found that 63.2% of patients were almost asymptomatic or had only mild symptoms, 15.8% were off all treatment, 28.1% were back on moclobemide, 10.6% were taking another psychotropic drug and 8.8% were in psychotherapy. All previous non-responders to moclobemide and mostly alcohol abusers (36.9%), had moderate or severe social phobia and were off all treatment (13.3%), on psychotherapy (15.9%) or on another psychotropic drug (8.8%). Discriminant analysis correctly predicted outcome in 93.5% of all patients. Alcohol abuse was by far the strongest predictor of negative outcome. Coexisting generalized anxiety disorder and dysthymia were less potent in this regard, whereas high baseline Hamilton anxiety or depression scale scores, circumscribed social phobia, or social phobia unassociated with avoidant personality disorder were predictors of a positive outcome. In conclusion, severe social phobia can be successfully treated in the long-term but many patients may need medication or psychotherapy for many years. Treatment should start as early as possible because complications such as alcohol abuse make treatment difficult.     

Hormone replacement therapy and other potential treatments for dementias

The past decade has seen a substantial increase in the number of individuals affected by dementia. Dementia places a tremendous personal and economic burden on millions of patients and caregivers annually. Consequently, many scientists have been searching for a treatment for dementia to avoid the imminent public health crisis that will occur if this trend continues. Primary and secondary prevention studies, as well as animal research, demonstrate the potential for hormone replacement therapy (HRT) as an efficacious treatment for dementia. Recently, the Women's Health Initiative-Memory Study began the first randomized, longterm clinical trial to test the hypothesized role of HRT at the onset and in the progression of dementia in women. Researchers also are investigating the potential of other treatments for dementias, such as nonsteroidal anti-inflammatory drugs and free radical scavengers.     

Adulthood functioning: the joint effects of parental alcoholism, gender and childhood socio-economic stress

The popular literature has publicized the adjustment difficulties of adult children of an alcohol-dependent parent (ACOAs); however, empirical studies do not provide consistent support. We examined the impact of parental alcoholism, degree of childhood socio-economic stress and gender on three broad categories of adulthood functioning (psychopathology, socio-economic attainment and marital stability). These effects were investigated with a heterogeneous sample of 400 men and 226 women participating in studies at the University of Michigan Alcohol Research Center. Parental alcoholism and childhood socio-economic stress exerted significant independent effects on most adulthood functioning measures. Men and women differed substantially only on socio-economic attainment measures, and effects of parental alcoholism and childhood economic stress on men and women were generally similar. For marital stability, parental alcoholism and childhood socio-economic stress interacted. These results suggest that researchers who study the impact of family history for alcoholism on psychological functioning should consider other aspects of the family of origin that promote wellbeing. In addition, results of this study point to the need for more research on gender differences, protective factors that promote good adjustment and outcome measures reflecting general life adaptation.     

Neutral endopeptidase activity in newborn and adult rabbit tracheas

Neutral endopeptidase (NEP, E.C. 3.4.24.11), a widely distributed ectoenzyme, cleaves and inactivates a variety of biologically active peptides, including the tachykinin, substance P (SP). This study was undertaken to determine whether the modulation of SP airway smooth muscle contraction by NEP is age-dependent. We studied the contractile response of isolated tracheal rings from newborn and 120 day old New Zealand white rabbits. We measured NEP activity and determined immunoreactive NEP content in tracheal membrane preparations. NEP activity was then localized histochemically in sections of rabbit tracheas. In the presence of the NEP inhibitor, SCH 32615, the contractile response of isolated tracheal rings to SP was increased both in the newborn and 120 day old rabbits. However, the increase was greatest in the newborn animals. NEP activity in tracheal membrane preparations increased fivefold between the newborn and 120 day old rabbits. Western blot analysis also revealed a significant increase in the immunoreactive NEP content of these tracheal membrane preparations between the newborn and 120 day old rabbits. NEP activity, localized histochemically, was most intense in the epithelial region of the newborn animals, with a shift of activity to the subepithelial region with age. The prominent epithelial localization of neutral endopeptidase in the tracheas of these 1 day old rabbits, which we have shown to have relatively low neutral endopeptidase activity, suggests that the location of neutral endopeptidase in the airway, including proximity to relevant substance P receptors, may be critical to its function.     

Biphasic subcellular localization of the DAZL-related protein boule in Drosophila spermatogenesis

The Drosophila boule gene is expressed exclusively in the male germline and encodes an RNA binding protein closely related to the mammalian fertility factors encoded by the DAZ (Deleted in Azoospermia) and DAZL (DAZ-like) genes. Mutation of boule blocks both meiotic divisions. Differentiation nonetheless continues, resulting in tetraploid spermatids that fail to mature into sperm. We have found that Boule localizes premeiotically to a perinucleolar region and then translocates to the cytoplasm at the onset of meiosis. We show that deletion of the Y chromosome ks-1 fertility locus eliminates Boule nuclear localization, although it does not perturb entry into meiosis. Based on these observations we propose that Boule acts in the cytoplasm to regulate the stability or translation of messenger RNA encoding an essential meiotic factor.     

Molecular ordering of apoptosis induced by anticancer drugs in neuroblastoma cells

Apoptosis mediated by anticancer drugs may involve activation of death-inducing ligand/receptor systems such as CD95 (APO-1/Fas), cleavage of caspases, and perturbance of mitochondrial functions. We investigated the sequence of these events in SHEP neuroblastoma cells transfected with Bcl-2 or Bcl-X(L) using two different drugs, namely, doxorubicin (Doxo), which activates the CD95/CD95 ligand (CD95-L) system, and betulinic acid (Bet A), which does not enhance the expression of CD95 or CD95-L and which, as shown here, directly targets mitochondria. Apoptosis induced by both drugs was inhibited by Bcl-2 or Bcl-X(L) overexpression or by bongkrekic acid, an agent that stabilizes mitochondrial membrane barrier function, suggesting a critical role for mitochondria. After Doxo treatment, enhanced CD95/CD95-L expression and caspase-8 activation were not blocked by Bcl-2 or Bcl-X(L) and were found in cells with a mitochondrial transmembrane potential (delta psi(m)) that was still normal (delta psi(m)high cells). In marked contrast, after Bet A treatment, caspase-8 activation occurred in a Bcl-2- or Bcl-X(L)-inhibitable fashion and was confined to cells that had lost their delta psi(m) (delta psi(m)low cells). Mitochondria from cells treated with either Doxo or Bet A induced cleavage of both caspase-8 and caspase-3 in cytosolic extracts. Thus, caspase-8 activation may occur upstream or downstream of mitochondria, depending on the apoptosis-initiating stimulus. In contrast to caspase-8, cleavage of caspase-3 or poly(ADP-ribose)polymerase was always restricted to delta psi(m)low cells, downstream of the Bcl-2- or Bcl-X(L)-controlled checkpoint of apoptosis. Cytochrome c, released from mitochondria undergoing permeability transition, activated caspase-3 but not caspase-8 in a cell-free system. However, both caspases were activated by apoptosis-inducing factor, indicating that the mechanism of caspase-8 activation differed from that of caspase-3 activation. Taken together, our findings demonstrate that perturbance of mitochondrial function constitutes a central coordinating event in drug-induced cell death.     

Complex intracranial aneurysms: combined operative and endovascular approaches

OBJECTIVE: Endovascular management of complex intracranial aneurysms is increasingly being considered as an alternative to standard surgical clipping. However, little attention has been paid to the complementary nature of surgery and endovascular therapy. METHODS: Between September 1992 and May 1997, 12 patients with complex intracranial aneurysms were treated with combined operative and endovascular methods. Seven patients demonstrated subarachnoid hemorrhage (two of Grade II, two of Grade III, and three of Grade IV). Five patients demonstrated unruptured aneurysms, i.e., three giant aneurysms (one vertebrobasilar junction aneurysm, one middle cerebral artery bifurcation aneurysm, and one internal carotid artery-ophthalmic artery aneurysm), one large internal carotid artery-ophthalmic artery aneurysm, and one middle cerebral artery serpentine aneurysm. Management strategies involved either surgery followed by endovascular therapy (S-E; n = 5) or endovascular therapy followed by surgery (E-S; n = 7). S-E paradigms included aneurysm exploration followed by endovascular treatment (S-E1; n = 3), partial aneurysm clipping followed by endovascular aneurysm packing (S-E2; n = 1), and extracranial-to-intracranial bypass followed by endovascular parent vessel occlusion (S-E3; n = 1). E-S paradigms included superselective angiography followed by surgical clipping (E-S1; n = 2), Guglielmi detachable coil partial dome packing followed by delayed surgical clipping (E-S2; n = 2), proximal temporary vessel balloon occlusion followed by aneurysm clipping (E-S3; n = 2), and proximal permanent vessel occlusion followed by surgical aneurysm decompression for mass effect treatment (E-S4; n = 1). RESULTS: Eleven aneurysms (92%) were completely eliminated. The remaining aneurysm was 90% obliterated and remained quiescent at the 34-month follow-up examination, despite presenting with subarachnoid hemorrhage. No patient experienced repeat bleeding (follow-up period, 23+/-28 mo). There were no deaths. One patient achieved a fair outcome (Glasgow Outcome Scale score of III); all other patients experienced excellent outcomes (Glasgow Outcome Scale score of I). In all cases, the aneurysm management paradigm chosen had a positive effect on definitive therapy. CONCLUSION: Several factors can contribute to the complexity of intracranial aneurysms. Management strategies that combine operative and endovascular techniques in a complementary way, for the best possible outcomes for these patients, can be designed accordingly.     

Middle latency auditory evoked potentials in epilepsy

Heparin (HE) exhibited a protective effect on liposome peroxidation induced by Fe2+ and Cu2+, decreasing the formation of both conjugated dienes and thiobarbituric acid reactive substances (TBARS) in a dose-dependent manner. The antioxidant activity was more relevant in the oxidizing system employing Fe2+ and H2O2 and generating the highly reactive OH radical. The analysis of liposome size distribution by quasielastic laser light scattering showed that: (1) the native structure of the particles was completely lost after exposure to Fenton reagent; (2) the presence of HE in the reaction mixture completely prevented the peroxidative damage on liposomes. Thus, HE acts as an antioxidant factor on membrane lipid bilayer. This suggests that HE, released from mast-cell granules during inflammatory processes, might locally protect the cell membrane from the oxidative injuries.