Loss of basal forebrain P75(NTR) immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease.

The long-held belief that degeneration of the cholinergic basal forebrain was central to Alzheimer's disease (AD) pathogenesis and occurred early in the disease process has been questioned recently. In this regard, changes in some cholinergic basal forebrain (CBF) markers (e.g. the high affinity trkA receptor) but not others (e.g., cortical choline acetyltransferase [ChAT] activity, the number of ChAT and vesicular acetylcholine transporter-immunoreactive neurons) suggest specific phenotypic changes, but not frank neuronal degeneration, early in the disease process. The present study examined the expression of the low affinity p75 neurotrophin receptor (p75(NTR)), an excellent marker of CBF neurons, in postmortem tissue derived from clinically well-characterized individuals who have been classified as having no cognitive impairment (NCI), mild cognitive impairment (MCI), and mild AD. Relative to NCI individuals, a significant and similar reduction in the number of nucleus basalis p75(NTR)-immunoreactive neurons was seen in individuals with MCI (38%) and mild AD (43%). The number of p75(NTR)-immunoreactive nucleus basalis neurons was significantly correlated with performance on the Mini-Mental State Exam, a Global Cognitive Test score, as well as some individual tests of working memory and attention. These data, together with previous reports, support the concept that phenotypic changes, but not frank neuronal degeneration, occur early in cognitive decline. Although there was no difference in p75(NTR) CBF cell reduction between MCI and AD, it remains to be determined whether these findings lend support to the hypothesis that MCI is a prodromal stage of AD.     

Body fat in normal adults estimated by oxygen-18- and deuterium-dilution and by anthropometry: a comparison

We estimated body fat in 20 normal adults (10 males and 10 females) from 18O- and 2H-dilution spaces and from the equations of Durnin & Womersley and Pollock, Schmidt & Jackson based on skinfold thickness measurements. Differences between methods for body fat estimation were found to be sex-dependent: subsequent analyses indicated significant differences between methods within each sex. Regardless of sex, the highest fat estimates were obtained with the 18O-dilution method, followed by those obtained with the 2H-dilution method or the Durnin & Womersley equation. The lowest fat estimates were obtained using the Pollock, Schmidt & Jackson equation. The 18O-dilution method and the Durnin & Wormersley anthropometric method are both suitable and appropriate for body fat estimation in adults studied under field conditions.     

Repair of large midline incisional hernias with polypropylene mesh: Comparison of three operative techniques

Polypropylene mesh is widely used for the reconstruction of incisional hernias that cannot be closed primarily. Several techniques have been advocated to implant the mesh. The objective of this study was to evaluate, retrospectively, early and late results of three different techniques, onlay, inlay, and underlay. The records of 53 consecutive patients with a large midline incisional hernia — 25 women and 28 men, mean age 60.4 (range 28–94) — were reviewed. Polypropylene mesh was implanted using the onlay technique in 13 patients, inlay in 23 patients, and underlay in 17 patients. Either the greater omentum or a polyglactin mesh was interponated between the mesh and the viscera. The records of these 53 patients were reviewed with respect to: size and cause of the hernia, pre- and postoperative mortality and morbidity, with special attention to wound complications. Patients were invited to attend the outpatient clinic at least 12 months after implantation of the mesh for physical examination of the abdominal wall. Postoperative complications occurred in 14 (26.4%) patients. The onlay technique had significantly more complications, as compared to both other techniques. Reherniation occurred in 15 (28.3%) patients. The reherniation rate of the inlay technique was significantly higher than after the underlay technique (44% vs 12%, P=0.03) and tended to be higher than the onlay technique (44% vs 23%, P=0.22). Repair of large midline incisional hernias with the use of a polypropylene mesh carries a high risk of complications and has a high reherniation rate. The underlay technique seems to be the better technique.     

Role of interleukin 6 in the growth of myeloma-derived cell lines.

The role of interleukin 6 (IL-6) in the growth of five multiple myeloma-derived cell lines was characterized. The U266 and RPMI 8226 cell lines demonstrated increased DNA synthesis when cultured with exogenous IL-6, expressed IL-6 cell surface receptors (IL-6Rs) and expressed mRNA for IL-6R. However, these cells did not secrete detectable IL-6 protein, and a neutralizing antibody to IL-6 did not inhibit their growth. Three other myeloma-derived cell lines ARH-77, IM-9 and HS-Sultan did not respond to exogenous IL-6, secrete IL-6 or express cell surface IL-6Rs. The IL-6 responsive cell lines bore late B-cell surface antigens (Ags), CD38 and PCA-1, whereas those lines which were non-IL-6 responsive strongly expressed B1 (CD20) and B4 (CD19) Ags, representing earlier stages in B-cell differentiation. Finally, the two IL-6 responsive cell lines did not express Epstein-Barr virus (EBV) proteins; in contrast, EBV encoded proteins typically expressed during latency could be detected in the three non-IL-6 responsive lines, confirming infection with virus. These studies clarify the heterogeneity observed in the myeloma cell line phenotype and biology and suggest that the U266 and RPMI 8226 cell lines, which express IL-6 cell surface receptors and are IL-6 responsive, may be useful for further study of IL-6 signal transduction in and related IL-6 mediated growth of myeloma in vivo. In contrast, those cell lines which are IL-6-independent provide a model for further study of EBV transformation and IL-6-dependent growth mechanisms in malignancy.     

Pretreatment of bone with osteoclasts affects phenotypic expression of osteoblast-like cells.

Implant surface morphology regulates osteoblast phenotypic expression. Osteoblast sensitivity to non-biologic surfaces suggests that native bone surface features may also affect osteoblast response. To test this, MG63 osteoblast-like cells were grown for 7 days on bovine cortical bone wafers pretreated with rat bone marrow osteoclasts for 0, 10 or 20 days. Response to osteoclast-treated surfaces was compared to the response of MG63 cells to titanium surfaces with smooth and rough microtopographies. Cell number, differentiation (alkaline phosphatase activity and osteocalcin levels), and local factors (PGE(2) and TGF-beta1) were measured in confluent cultures. Compared to culture on plastic, cell number was reduced on all three types of bone wafers; this effect was dose-dependent with increasing resorption of the surface. Alkaline phosphatase specific activity was increased (P相似文献   

Nonheme iron in sickle erythrocyte membranes: association with phospholipids and potential role in lipid peroxidation

Previous studies documented the abnormal association of heme and heme proteins with the sickle RBC membrane. We have now examined RBC ghosts and inside-out membranes (IOM) for the presence of nonheme iron as detected by its formation of a colored complex with ferrozine. Sickle ghosts have 33.8 +/- 18.2 nmol nonheme iron/mg membrane protein, and sickle IOM have 4.3 +/- 3.0 nmol/mg. In contrast, normal RBC ghosts and IOM have no detectable nonheme iron. The combination of heme and nonheme iron in sickle IOM averages nine times the amount of membrane- associated iron in normal IOM. Kinetics of the ferrozine reaction show that some of this nonheme iron on IOM reacts slowly and is probably in the form of ferritin, but most (72% +/- 18%) reacts rapidly and is in the form of some other biologic chelate. The latter iron compartment is removed by deferoxamine and by treatment of IOM with phospholipase D, which suggests that it represents an abnormal association of iron with polar head groups of aminophospholipids. The biologic feasibility of such a chelate was demonstrated by using an admixture of iron with model liposomes. Even in the presence of tenfold excess adenosine diphosphate, iron partitions readily into phosphatidylserine liposomes; there is no detectable association with phosphatidylcholine liposomes. To examine the bioavailability of membrane iron, we admixed membranes and t-butylhydroperoxide and found that sickle membranes show a tenfold greater peroxidation response than do normal membranes. This is not due simply to a deficiency of vitamin E, and this is profoundly inhibited by deferoxamine. Thus, while thiol oxidation in sickle membranes previously was shown to correlate with heme iron, the present data suggest that lipid peroxidation is related to nonheme iron. In control studies, we did not find this pathologic association of nonferritin, nonheme iron with IOM prepared from sickle trait, high-reticulocyte, postsplenectomy, or iron-overloaded individuals. These data provide additional support for the concept that iron decompartmentalization is a characteristic of sickle RBCs.     

Use of protein A immunoadsorption as a treatment for thrombocytopenia in HIV-infected homosexual men: a retrospective evaluation of 37 cases.

Thirty-seven HIV-infected homosexual men with thrombocytopenia (less than 100 x 10(9)/l) received protein A immunoadsorption treatments to remove platelet-sensitizing immunoglobulin (Ig) G and circulating immune complexes (CIC) from plasma. Patients received an average of six treatments each, consisting of 250 ml plasma over a 3-week period. Clinical improvement in hemorrhagic symptoms associated with substantial increase in platelet counts was achieved in 18 patients. These responses were maintained over a median follow-up period of more than 7 months in 14 evaluable patients who were not lost to follow-up (three patients relapsed in 2 weeks and one received another therapy). Generally, moderate transient treatment-related side-effects included fever, musculoskeletal pain, chills and nausea. A transient serum sickness-like reaction was observed in seven patients, leading to termination of treatment in two. Clinical responses were associated with significant decreases in levels of platelet-sensitizing Ig, including CIC. Stimulation of broadly cross-reactive anti-antigen-binding fragment [F(ab)2], antibodies contributed to these responses. Protein A immunoadsorption is an effective alternative treatment for HIV-associated thrombocytopenia.