Autosomal dominant dementia with widespread neurofibrillary tangles

Several familial dementing conditions with atypical features have been characterized, but only rarely is the neuropathology dominated solely by neurofibrillary lesions. We present a Midwestern American pedigree spanning four generations in which 15 individuals were affected by early-onset dementia with long disease duration, with an autosomal dominant inheritance pattern, and with tau-rich neurofibrillary pathology found in the brain post mortem. The average age at presentation was 55 years with gradual onset and progression of memory loss and personality change. After 30 years' disease duration, the proband's neuropathologic examination demonstrated abundant intraneuronal neurofibrillary tangles (NFTs) involving the hippocampus, pallidum, subthalamic nucleus, substantia nigra, pons, and medulla. Only sparse neocortical tangles were present and amyloid plaques were absent. The tangles were recognized by antibodies specific for phosphorylation-independent (Tau-2, T46, 133, and Alz-50) and phosphorylation-dependent epitopes (AT8, T3P, PHF-1, 12E8, AT6, AT18, AT30) in tau proteins. Electron microscopy of NFTs in the dentate gyrus and midbrain demonstrated paired helical filaments. Although the clinical phenotype resembles Alzheimer's disease, and the neuropathologic phenotype resembles progressive supranuclear palsy, an alternative consideration is that this familial disorder may be a new or distinct disease entity.     

Scanning electron microscopy and immunohistochemical observations of the vascular nerve plexuses in the dental pulp of rat incisor

Elimination of auditory nerve activity results in atrophy and death of nucleus magnocellularis (NM) neurons in the chick. One early event in the degeneration of NM neurons is a disruption of their ribosomes. This experiment examines the role of metabotropic glutamate receptors in afferent regulation of ribosomes. The auditory nerve on one side of a chick brainstem slice was stimulated in vitro. Rapid stimulation-dependent changes in ribosomes were visualized by immunolabeling using an antibody, called Y10B, that recognizes ribosomal RNA. In normal media, NM neurons on the stimulated side of the slice show greater Y10B labeling than the unstimulated NM neurons on the opposite side of the same slice. The role of metabotropic glutamate receptors was evaluated by unilaterally stimulating the auditory nerve in media containing the metabotropic glutamate receptor antagonist (RS)-alpha-methyl-4-carboxyphenyl-glycine (MCPG). Addition of MCPG to the bath did not block EPSPs produced by stimulating the auditory nerve. However, MCPG did prevent the stimulation-dependent regulation of ribosomes in NM neurons (as indexed by Y10B labeling). These data suggest that glutamate may play a trophic role in the young auditory system through activation of metabotropic glutamate receptors.     

Pulmonary function and respiratory symptoms in forest firefighters

As part of a national study of surgical departments is Israel, cardiac surgery patients undergoing open heart surgery between 1987 and 1989 were followed-up prospectively. Of these, 1,046 patients had coronary artery bypass grafting (CABG) and are the subject of this report. The six-months mortality after surgery was 12.9% among 202 women and 4.1% among 844 men. Female gender was an independent predictor of mortality even after controlling for the effect of 14 putative risk factors. The adjusted relative risk for mortality in women compared to men was 2.79 (1.5-5.2). In an attempt to understand this excessive mortality among women, a detailed analysis in one of the participating hospitals revealed differences associated with surgical technique by gender, such as proportion of patients with entirely venous grafting vs internal mammary artery grafts (IMA). Thirty percent of women vs 4.8% of men had entirely venous grafting. Adjusting the data for differences in the proportion of venous grafting has obliterated the difference in mortality between the genders in that hospital. We suggest that interventions to reduce mortality among women should involve a more careful choice of female candidates for CABG surgery, as well as introduction of modifications in the operating technique.     

Long-term results of the Stamey bladder neck suspension: direct comparison with the Marshall-Marchetti-Krantz procedure

Non-glycosylated recombinant Locusta migratoria apolipophorin-III, apoLp-III, was expressed in E. coli and its physical-chemical properties were compared to those of the glycosylated native apoLp-III. Fluorescence quantum yield and acrylamide quenching studies indicated a slightly higher accessibility of the Trp residues in the recombinant apoLp-III. Far-UV CD spectroscopy indicated that the recombinant apoLp-III has a lower alpha-helical content than the glycosylated apoLp-III. Both proteins spontaneously formed discoidal recombinant lipoprotein particles when incubated with dimyristoylphosphatidylcholine (DMPC). Interaction with lipid promotes an increase in alpha-helical content. CD and fluorescence studies indicate that both proteins adopt the same conformation in the lipid-bound state. However, the kinetics of association of the recombinant protein with DMPC is 5-fold faster than that of the native protein. The results suggest that glycosylation inhibits the lipid binding activity by preventing the exposure of hydrophobic domains and/or decreasing the conformational flexibility of the protein.