Hydrogen peroxide induces transient dephosphorylation of tau protein in cultured rat oligodendrocytes.

Oxidative stress is a major mediator of neurodegeneration. In this study, we tested the effects of oxidative stress induced by a brief exposure to hydrogen peroxide (H(2)O(2)) on the phosphorylation state of the tau protein in oligodendrocytes (OL). Primary oligodendrocyte cultures prepared from newborn rat brains were exposed to millimolar concentrations of H(2)O(2) for up to 15 min, and then incubated in normal medium for up to 12 h. The treatment caused morphological degeneration of OL characterized by the loss of cellular processes apparent approximately 3 h after H(2)O(2) exposure. The morphological degeneration was preceded by a profound dephosphorylation of tau protein revealed by immunoblot using monoclonal tau-1 antibody that recognizes the dephosphorylated epitope. The dephosphorylated form increased dramatically during H(2)O(2) exposure, peaked after 2 h of post-exposure, and returned to the baseline level within 12 h. Total tau protein levels were not changed in the course of the experiment as judged by immunoblotting with phosphorylation-insensitive tau-5 and 46-1 monoclonal antibodies. Our finding demonstrates that oxidative stress induces a rapid but transient dephosphorylation of tau protein that may underlie morphological degeneration of OL.

Neu differentiation factor regulates tau protein and mRNA in cultured neonatal oligodendrocytes.

Axonal signals activate myelinogenesis via regulation of the extent to which oligodendrocyte (OLG) processes wrap around the axon. The cytoskeleton in OLG processes is actively involved in myelination and is a putative target for axonal regulation of myelination. The axon-associated neuregulins may regulate the cytoskeleton extensions in OLG processes. Here, we report that the neuregulin neu differentiation factor (NDF) increases the expression of tau mRNA and tau protein in OLGs. Treatment of neonatal OLGs with alpha-NDF or beta-NDF resulted in dramatic increases in the length of OLG processes, which appeared either as singular unbranched extensions or as a network of extensively branched processes. By immunoblot analysis with tau-1 mAb, which recognizes the dephosphorylated form of the tau proteins, neonatal OLGs treated with alpha-NDF or beta-NDF, had an increase in tau protein levels. The increase of tau levels in beta-NDF-treated cells is much greater than the twofold increase present in alpha-NDF-treated cells. By immunoblot analysis with the phosphorylation-insensitive tau-5 mAb, beta-NDF-treated cells had a twofold increase in tau. Immunoblot analysis suggest that alpha-NDF and beta-NDF promote a twofold increase in the tau protein levels in OLG, with the beta-factor also promoting a tau dephosphorylation. Using promoters spanning the amino-terminal region of tau, we found that OLGs treated with alpha-NDF or beta-NDF contained approximately twofold more tau mRNA than untreated cells. However, there was no qualitative difference between control and NDF-treated cells in the pattern of tau mRNA isoforms expressed. A model is proposed in which the axonal NDF-induced regulation of tau expression in OLGs may be part of the mechanism by which the axon regulates myelination.

Fiber-optic sensor system for rapid positioning of a microelectrode array.

A fiber-optic intensity sensor has been developed for vertically positioning microelectrode arrays above the retina of a live frog. Closely spaced fibers illuminate and collect reflections from the retinal surface, and the output is electronically processed to drive an automated positioning circuit. Experimental and theoretical evaluations of fiber types and separation for both specular and diffuse reflectors, in vitro and in vivo, are presented, and multimode fibers on 125-mum centers are chosen for retinal experimentation. The sensor has applications in assessing spatial selectivity of stimulation of a multielectrode array and may be adaptable for lateral positioning.

Case report: severe microcytosis associated with the anemia of chronic disease.

When microcytosis is present in patients with anemia of chronic disease, the mean corpuscular volume (MCV) rarely if ever falls below 70 fL. The lowest MCV previously reported is 67 fL. We describe a patient with anemia of chronic disease with severe microcytosis and an MCV of 61 fL. After correction of the chronic disorder, complete correction of the hematologic values occurred. In patients with a low total iron binding capacity, iron therapy should not be instituted without clearly establishing the presence of iron deficiency irrespective of the degree of microcytosis.

Resected sigmoid carcinoma with 13-year metastasis-free interval. Sternal recurrence detected by immunoscintigraphy.

Colorectal cancers rarely present with bone metastases. Regular postoperative monitoring after resection by conventional imaging techniques and carcinoembryonic antigen levels aids physicians in identifying such tumor recurrences. However, some recurrences might elude detection by bone scan, computed tomography, and magnetic resonance imaging, and newer tests such as immunoscintigraphy using radioimmune-tagged monoclonal antibodies may be more diagnostic. Here we report a case, presenting with delayed recurrence at a rare bony site, in which application of immunoscintigraphy helped in the definitive detection of the tumor recurrence.

Functional implications for the microtubule-associated protein tau: localization in oligodendrocytes.

We present evidence that the microtubule-associated protein tau is present in oligodendrocytes (OLGs), the central nervous system cells that make myelin. By showing that tau is distributed in a pattern similar to that of myelin basic protein, our results suggest a possible involvement of tau in some aspect of myelination. Tau protein has been identified in OLGs in situ and in vitro. In interfascicular OLGs, tau localization, revealed by monoclonal antibody Tau-5, was confined to the cell somata. However, in cultured ovine OLGs with an exuberant network of processes, tau was detected in cell somata, cellular processes, and membrane expansions at the tips of these processes. Moreover, in such cultures, tau appeared localized adjacent to or coincident with myelin basic protein in membrane expansions along and at the ends of the cellular processes. The presence of tau mRNA was documented using fluorescence in situ hybridization. The distribution of the tau mRNA was similar to that of the tau protein. Western blot analysis of cultured OLGs showed the presence of many tau isoforms. Together, these results demonstrate that tau is a genuine oligodendrocyte protein and pave the way for determining its functional role in these cells.

Target specificity and size of avian sensory neurons supported in vitro by nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3.

To obtain insight into which subpopulations of sensory neurons in dorsal root ganglia are supported by different neurotrophins, we retrogradely labeled cutaneous and muscle afferents in embryonic day 9 chick embryos and followed their survival in neuron-enriched cultures supplemented with either nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), or neurotrophin-3 (NT-3). We found that NGF is a wide survival factor for subpopulations of both cutaneous and muscle afferents, whereas the survival effects of BDNF and NT-3 are restricted primarily to muscle afferents. We also measured soma size in each neurotrophic factor. These new data show that BDNF- and NT-3-dependent cells appear to be a mixture of two populations of neurons: one small diameter and the other large diameter. In contrast, based on size alone, NGF-dependent cells appear to be a single population of only small-diameter neurons. Thus, BDNF and NT-3 may have some new, previously unreported effects on small-diameter afferent neurons.

Gastrointestinal histoplasmosis in HIV infection: two cases of colonic pseudocancer and review of the literature.

Primary gastrointestinal infection is an uncommon manifestation of histoplasmosis. It is almost always associated with disseminated disease and/or an immunocompromised host. The ileum and cecum are the most common sites involved. We report two cases of primary gastrointestinal histoplasmosis in HIV-seropositive men who presented with annular constricting right colon lesions.

Observation of optical limiting and backscattering of nanosecond laser pulses in liquid-crystal fibers.

We report the recent observation of nonlinear-optical phenomena occurring in isotropic liquid-crystal-cored optical fibers, including passive all-optical self-limiting effects, stimulated backscattering, and phase conjugation. These processes occur at relatively low thresholds and short fiber lengths.

Neuronal differentiation triggered by blocking cell proliferation.

Treatment of the neuroblastoma cell line SHSY5Y with nerve growth factor (NGF) resulted in limited neurite extension, but proliferation continued. However, SHSY5Y cells treated with NGF and a pulse of the DNA polymerase alpha and delta inhibitor aphidicolin showed dramatic neuronal differentiation. Few differentiated cells were observed immediately following the NGF-aphidicolin treatment; however, continued treatment of the cells with NGF in the ensuing week resulted in extension of long neurites (> 400 microns). Neurite extension was not observed for cells treated with aphidicolin alone. Hence, aphidicolin and NGF act synergistically to induce differentiation of SHSY5Y cells. If maintained in NGF, the differentiated cells were stable for at least 1 month and displayed many neuronal characteristics. They were mitotically inactive, and, in contrast to control or NGF-treated cells, the differentiated cells required NGF for survival. The cells expressed multiple microtubule-associated proteins (MAP), including MAP 1A, MAP 1B, and tau. There was expression of synaptic vesicle antigens synaptophysin and SV2, but not synapsin Ia/b or synapsin IIa/b. Both hydroxyurea and thymidine, which inhibit synthesis of nucleotides, act synergistically with NGF to induce differentiation of SHSY5Y cells. Since aphidicolin, hydroxyurea, and thymidine are chemically unrelated, we conclude that these drugs enhance NGF-induced differentiation by blocking cell proliferation and not through an unrelated side effect. The model suggested by these studies is that differentiation is triggered by two simultaneous signals: NGF and cessation of cell proliferation.

Adult foregut duplication.

We report a gastric duplication in a 23-year-old man. The case is unique because the stomach is the rarest location for enteric duplication, the duplication almost never occurs in adults, and the duplication consisted exclusively of pancreatic tissue. This extreme example illustrates the close embryologic and anatomic association between stomach and pancreas. A case is made for the use of the general term of foregut duplication to avoid confusing nomenclature.

Direct determination of creatine kinase equilibrium constants with creatine or cyclocreatine substrate.

The equilibrium constants of two reactions catalyzed by rabbit muscle creatine kinase with creatine or cyclocreatine as substrate were determined by 31P-NMR. The value of the equilibrium constant with creatine as substrate was 172.10(7) M(-1) in agreement with previous work (Veech, R.L., Lawson, J.W.R., Cornell, W. and Krebs, H.A. (1979) J. Biol. Chem 254, 6538-6547). The value with cyclocreatine was 5.62.10(7) M(-1) and the ratio of the two constants is 30.6. It was possible to determine the ratio of the two equilibrium constants in a reaction mixture containing both substrates since it was found that the 31P resonances of P-creatine and P-cyclocreatine were well resolved. The ratio of K1/K2 determined in such experiments was 34.6, of the same order as previously reported by Annesley and Walker (Annesley, T.M. and Walker, J.B. (1977) Biochem. Biophys. Res. Commun. 74, 185-190).

Synchronous cancers of the colon and rectum: report of eight cases.

This study reviews eight patients collected over a period of 3 yr with synchronous primary adenocarcinomas with special emphasis on presentation of illness, diagnosis, location of tumors, and their association with benign polyps. All of the synchronous carcinomas in this study were located in different surgical segments and all associated benign polyps were located in the same surgical segments. Workup included colonoscopy followed by completion of colon examination by barium enema. All patients underwent surgical resection of their tumors. It is therefore concluded that the incidence their tumors. It is therefore concluded that the incidence of synchronous tumors of the large colon is high enough to warrant total colon examination either by colonoscopy or barium enema.

Acne vulgaris aggravated by sunlight.

The symptoms of approximately 3 percent of our patients with acne vulgaris worsen during the summer months even though they maintain previously effective therapy. We show herein that the addition of 5 percent para-aminobenzoic acid (PABA) in alcohol (used as a sunscreen) resulted in marked improvement in their ability to tolerate sunlight. This condition, acne vulgaris aggravated by sunlight, has been compared to acne aestivalis which is another sunlight-induced disorder.

Congenital duodenal stenosis. The duodenal cervix sign.

A case of congenital duodenal stenosis is reported complicated by recurrent pancreatitis. The diagnosis was not initially entertained because of the pancreatitis. The radiographic appearance on gastrointestinal series was unusual for pancreatitis. The finding of an anomalous celiac axis on arteriography suggested the possibility of other congenital anomalies. The diagnosis of congenital duodenal stenosis was confirmed at laparotomy. The obstruction was relieved with a duodenojejunostomy. Two year follow-up reveals the patient to be asymptomatic without recurrence of pancreatitis. This is the first endoscopic report of this lesion and the presence of the duodenal cervix sign should suggest the diagnosis of congenital duodenal stenosis.