The role of physician house calls in comprehensive ambulatory care.
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Aged↗
Biomedical subjects
D Muller
Publications and source records attributed to D Muller.
Sequential Adsorption of Human Serum Albumin (HSA), Immunoglobulin G (IgG), and Fibrinogen (Fgn) at HMDSO Plasma Polymer Surfaces
The sequential adsorption of human serum albumin (HSA), immunoglobulin G (IgG), and fibrinogen (Fgn) at hexamethyldisiloxane (HMDSO) plasma polymer surfaces was investigated with ellipsometry and total internal reflection fluorescence spectroscopy (TIRF) as a function of adsorption time, pH, and excess electrolyte concentration. HSA was found to self-exchange very slowly ( approximately hours) at pH 7.2, irrespective of adsorption time in the range 90 s to 90 min. Preadsorbed HSA was exchanged by Fgn and IgG only to a limited extent irrespectively of pH (5 </= pH </= 8) and excess electrolyte concentration (5 mM </= Cs </= 150 mM). At an excess electrolyte concentration of 150 mM, the sequential adsorption of Fgn and IgG was dramatically reduced by HSA preadsorption, irrespective of pH. At an excess electrolyte concentration of 5 mM, on the other hand, there were indications of second-layer adsorption of Fgn and IgG. Copyright 1997Academic Press
Journal Article↗
Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation.
Long-term potentiation (LTP), a cellular model of learning and memory, requires calcium-dependent protein kinases. Induction of LTP increased the phosphorus-32 labeling of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPA-Rs), which mediate rapid excitatory synaptic transmission. This AMPA-R phosphorylation appeared to be catalyzed by Ca2+- and calmodulin-dependent protein kinase II (CaM-KII): (i) it correlated with the activation and autophosphorylation of CaM-KII, (ii) it was blocked by the CaM-KII inhibitor KN-62, and (iii) its phosphorus-32 peptide map was the same as that of GluR1 coexpressed with activated CaM-KII in HEK-293 cells. This covalent modulation of AMPA-Rs in LTP provides a postsynaptic molecular mechanism for synaptic plasticity.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
MLN64 exhibits homology with the steroidogenic acute regulatory protein (STAR) and is over-expressed in human breast carcinomas.
The MLN64 gene, which is localized in q12-q21 of the human chromosome 17, encodes a novel protein containing 2 distinct domains. At the N-terminal, MLN64 exhibits a potential trans-membrane region, while at the C-terminal, it shares homology with the F26F4.4 protein of Coenorhabditis elegans and the steroidogenic acute regulatory (StAR) protein, a mitochondrial protein which is involved in steroid-hormone synthesis. By comparing the C-terminal part of these proteins, we defined a novel protein domain, which we termed SHD for "StAR Homology Domain". Of the 93 primary invasive breast carcinomas that were examined, 14 were found to over-express MLN64. These 14 tumors also expressed high c-erbB-2 transcript levels, which were not detected in the MLN64-negative tumors. MLN64 mRNA and protein were specifically detected in malignant cells of breast carcinomas. MLN64 protein was localized within bundle-like structures distributed throughout the cell cytoplasm and condensed in a perinuclear patch, suggesting an association with a specific cell compartment. When the N-terminal part of MLN64 was deleted, MLN64 was uniformly distributed in the cell cytoplasm, indicating that N-terminal part is involved in the specific cytoplasmic localization of MLN64. The homology between the C-terminal part of MLN64 and the functional StAR domain (SHD) suggests that MLN64 and StAR, although distributed in different cellular compartments, may both play a role in steroidogenesis. In this case, the high levels of MLN64 observed in some breast carcinomas could contribute to the progression of these tumors through increased intratumoral steroidogenesis.
Amino Acid Sequence↗
Staurosporine but not chelerythrine inhibits regeneration in hippocampal organotypic cultures.
A mechanical lesion in hippocampal organotypic cultures is followed by a recovery process involving scar formation, sprouting of fibres and formation of new functional synapses. Here we tested the effect of staurosporine and chelerythrine, two protein kinase C (PKC) inhibitors, on this lesion-induced neurite outgrowth of Shaffer collaterals. At a concentration of 1 microM, staurosporine delayed functional recovery assessed by measuring synaptic field potentials across the lesion, without altering synaptic transmission on nonlesioned cultures. Immunostaining carried out by using antibodies directed against neurofilament proteins showed that there was a marked reduction in the number of regenerating fibres crossing the lesion. In contrast to this, chelerythrine (50 microM) did not prevent functional recovery, although it affected synaptic transmission and plasticity at this concentration. We conclude that the inhibition of sprouting produced by staurosporine is independent of its blockade of PKC-mediated phosphorylation mechanisms.
Alkaloids↗
Adsorption of immunoglobulin G and anti-factor VIII inhibitory antibody from haemophiliac plasma to derivatized polystyrenes.
Modified polystyrene resins containing sulphonate groups and tyrosyl sulphamide or tyrosyl methyl ester sulphamide groups have been investigated with respect to their potential for selective binding of anti-Factor VIII inhibitory antibodies from plasma. Adsorption of total immunoglobulin G and of a monoclonal antibody to Factor VIII was measured following addition of the radioiodinated proteins to normal plasma, plasma depleted of Factor VIII by adsorption on a resin coupled to anti-Factor VIII antibody, and haemophiliac plasma containing various levels of inhibitory anti-Factor VIII antibody. Depletion of anti-Factor VIII antibody from the haemophiliac plasmas by incubation with the resins was also measured by Bethesda assay. The modified resins and their corresponding unmodified "controls' showed similar binding of total immunoglobulin G. However, only resins containing either sulphonate or a combination of sulphonate and tyrosyl sulphamide groups showed evidence of selective adsorption of anti-Factor VIII antibody from plasma.
Adsorption↗
Sprouting and functional recovery in co-cultures between old and young hippocampal organotypic slices.
We developed a model of lesion of Schaffer collaterals in hippocampal organotypic slice cultures to analyse the capacity for sprouting and functional recovery expressed in young (one week old) and old (four week old) slice cultures. Slice cultures were sectioned at different ages of maturation in two separate half-slices and maintained in co-culture. Functional recovery was assessed by measuring synaptic responses elicited across the lesion seven days after the lesion and sprouting was evaluated by biocytin labeling of the regenerating fibers seen under the same conditions. Sprouting and functional recovery were found to be markedly reduced and delayed in old vs young cultures. Preparation of co-cultures between young CA3 and old CA1 half-slices resulted in a significant reduction in the capacity for sprouting and regeneration of the young CA3 neurons. Conversely, co-cultures prepared between old CA3 and young CA1 half-slices showed a markedly enhanced capacity for sprouting and functional recovery of old CA3 neurons. These results indicate that the age-dependent impairment in sprouting and regeneration expressed in cortical regions can be improved by and depends upon the presence of a favourable environment.
Animals↗
Amplification of 11q13 DNA markers in head and neck squamous cell carcinomas: correlation with clinical outcome.
This study was performed on 282 patients with primary head and neck squamous cell carcinomas to evaluate the prognostic importance of 11q13 amplification. Amplification of the 11q13 DNA markers, HST-1/FGF-4 and BCL-1, evaluated by Southern and slot blot hybridisation, was detected in 52% of tumours. 11q13 amplification was associated with tumour site since this alteration occurred in 76% of tumours arising in the hypopharynx, versus 40% in the other sites (P = 0.0007). 11q13 amplification was also significantly related to the presence of involved neck lymph nodes (P = 0.013). The relationship between 11q13 amplification and risk of progression was studied in two subgroups of head and neck cancer patients with regard to treatment modalities. The presence of 11q13 amplification in the tumour was not significantly associated with a shorter event-free survival (P = 0.82) and crude survival (P = 0.61) of the 201 patients treated by surgery and postoperative radiotherapy. Similarly, absence of a relationship was observed for the group of 79 patients treated by surgery alone. These results confirm that 11q13 amplification is a prominent event in head and neck squamous cell carcinoma, indicating that it may be a common genetic event in the development of these neoplasms, but is not a reliable prognostic marker.
Adult↗
Internal medicine residents' assessment of the subspecialty fellowship application process.
PURPOSE: The application process for fellowships in internal medicine subspecialties begins approximately 18 to 24 months before the start of training, requiring residents to decide on a career by the beginning of their second year of residency. The authors surveyed the internal medicine residents at Mount Sinai Hospital to assess their attitudes toward the fellowship application process. METHOD: A survey instrument was designed and given to all 121 residents in 1994-95. The instrument surveyed the residents' career plans and the timing of their decisions, inquired about the effect on their residency of applying for a fellowship, and asked the residents to assess and comment on the timing of the fellowship application process. RESULTS: In all, 80% (97) of the residents responded. Nearly two-thirds intended to apply for fellowship training; however, 17% of the first-year residents had changed their minds about their fellowship plans, and 50% of the second- and third-year residents had changed career plans. Whereas 79% of the first-year residents intended to apply "on time" during their second year, only 29% of the second-year residents intended to do so; 25% of the third-year residents planned to delay entry into a fellowship. Nearly two-thirds of the first- and second-year residents felt uncomfortable making an informed fellowship decision in their second year. In all, 60% of the residents felt they had to do research in order to get a competitive fellowship, and 68% said they had to change their assigned residency schedule to "get credentials" for fellowship applications. The consensus of nearly all the residents was that the timing of fellowship applications was much too early and should be moved to the middle of the third year. CONCLUSION: As the current system of applying for medical fellowships is generally experienced negatively by residents, the authors recommend that the process be moved to the middle of the third year and that medical schools, residency programs, and fellowship training programs reconsider the entire fellowship application process.
Attitude of Health Personnel↗
Vaccination against persistent viral infection exacerbates CD4+ T-cell-mediated immunopathological disease.
Lymphocytic choriomeningitis virus (LCMV) infection of normal mice results in a fatal immunopathologic meningitis mediated by CD8+ cytotoxic T lymphocytes (CTL). We have previously shown that female beta2-microglobulin-deficient (beta2m-/-) mice, which are also deficient in CD8+ T cells, are susceptible to LCMV-induced immune-mediated meningitis, characterized by significant weight loss and mortality. This LCMV disease in beta2m-/- mice is mediated by CD4+ T lymphocytes. Our previous studies have also demonstrated that male beta2m-/- mice are less susceptible than female beta2m-/- mice to LCMV-induced, immune-mediated mortality and weight loss. In this report, we show that vaccination of male beta2m-/- mice enhances immunopathology following intracranial infection with LCMV. We observed increased production of gamma interferon (IFN-gamma), an increase in CD4+ CTL precursor frequency, and an increased frequency of IFN-gamma-producing cells from spleen cells of vaccinated male beta2m-/- mice. Vaccinated male beta2m-/- mice also had significantly increased inflammation in the cerebrospinal fluid (CSF), characterized by a large CD4+ T-cell infiltrate. CSF cells from vaccinated mice showed increased production of IFN-gamma on day 7 postchallenge. Neither vaccinated nor control beta2m-/- mice were able to clear virus, and the two groups had similarly high levels of virus early after infection. These results suggest that the magnitude of the early immune response is more important than the level of virus in the brain in determining the outcome of immunopathology in beta2m-/- mice. We show here that vaccination can increase CD4+ T-cell-dependent immunopathology to a persistent viral infection.
Animals↗
Increased yield of plasmid DNA during removal of CsCl by ethanol precipitation.
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Cesium↗
The Gln223Arg and Lys656Asn polymorphisms in the human leptin receptor do not associate with traits related to obesity.
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Adult↗
Does pharmaceutical marketing actually have real and proven value?
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Advertising↗
Altered kinetics of CD4+ T cell proliferation and interferon-gamma production in the absence of CD8+ T lymphocytes in virus-infected beta2-microglobulin-deficient mice.
CD8+ T cells are the major mediators of cytotoxic T cell activity controlling viral infections in normal mice. CD8+ T cells have also been implicated in regulating the activity of other immune cells. We have examined the possible regulatory role of CD8+ T cells on CD4+ T cells by comparing immune responses in mice expressing normal CD8+ T cell responses and in CD8+ T cell-deficient beta2-microglobulin "knockout" mice. In normal mice, infection with lymphocytic choriomeningitis virus (LCMV) results in a biphasic T cell immune response. First, CD8+ T cells proliferate and produce interferon-gamma (IFN-gamma), and then 2 to 4 days later CD4+ T cells proliferate and produce IFN-gamma. CD8+ T cell activity is not detected during LCMV infection in beta2-microglobulin-deficient mice. However, in beta2-microglobulin-deficient mice the CD4+ T cell expansion is exaggerated and occurs 2 days earlier than observed in normal mice. Furthermore, the CD4+ T cells have substantial cytotoxic activity, which is not observed in the CD4+ T cell population in normal mice. However, CD4+ T cell IFN-gamma production in beta2-microglobulin-deficient mice lags behind the proliferative response, resulting in a relative delay in overall T cell IFN-gamma production compared to normal mice. Taken together, these data suggest that CD8+ T cell activation peaks at an earlier time point than CD4+ T cell activation during the primary immune response to LCMV and that CD8+ T cells may inhibit CD4+ T cell proliferation and the development of CD4+ T cell cytotoxic activity.
Animals↗
Induction of long-term potentiation is associated with major ultrastructural changes of activated synapses.
Long-term potentiation (LTP), an increase in synaptic efficacy believed to underlie learning and memory mechanisms, has been proposed to involve structural modifications of synapses. Precise identification of the morphological changes associated with LTP has however been hindered by the difficulty in distinguishing potentiated or activated from nonstimulated synapses. Here we used a cytochemical method that allowed detection in CA1 hippocampus at the electron microscopy level of a stimulation-specific, D-AP5-sensitive accumulation of calcium in postsynaptic spines and presynaptic terminals following application of high-frequency trains. Morphometric analyses carried out 30-40 min after LTP induction revealed dramatic ultrastructural differences between labeled and nonlabeled synapses. The majority of labeled synapses (60%) exhibited perforated postsynaptic densities, whereas this proportion was only 20% in nonlabeled synaptic contacts. Labeled synaptic profiles were also characterized by a larger apposition zone between pre- and postsynaptic structures, longer postsynaptic densities, and enlarged spine profiles. These results add strong support to the idea that ultrastructural modifications and specifically an increase in perforated synapses are associated with LTP induction in field CA1 of hippocampus and they suggest that a majority of activated contacts may exhibit such changes.
2-Amino-5-phosphonovalerate↗
Affinity of mouse immunoglobulin G subclasses for sialic acid derivatives immobilized on dextran-coated supports.
High-performance liquid affinity chromatography is a powerful method for the purification of biological compounds owing to its specificity, rapidity and high resolution. In our laboratory, we develop chromatographic supports based on porous silica beads. However, in order to minimize non-specific interactions between the inorganic surface and proteins in aqueous solution, the silica beads are coated with modified dextran. As previously reported, many affinity ligands can be covalently grafted onto dextran-coated silica. In this study, N-acetylneuramic acid, which belongs to the sialic acid family and is present in immunoglobulin G (IgG) epitopes, is used as an active ligand. The interactions of this affinity support and IgG subclasses are analyzed. This immobilized ligand enables purification of IgG3 antibodies.
Animals↗
High-performance liquid chromatographic assay for tryptase based on the hydrolysis of dansyl-vasoactive intestinal peptide.
A rapid, sensitive, semiautomated method to measure the activity of mast cell-derived tryptase has been developed. The assay is based on the tryptase-mediated hydrolysis of vasoactive intestinal peptide that was modified to include an N-terminal dansyl reporter group. Tryptase cleaves vasoactive intestinal peptide (VIP) producing two major and two minor products. Full-length VIP was separated from the proteolysis products by reverse-phase (C18) chromatography. The amount of each product as well as the amount of full-length substrate remaining was determined using an in-line fluorescence detector. As little as 0.5 pmol of peptide could be detected. Predominant cleavages were after Arg-14 and Lys-20 with minor cleavages after Lys-15 and Lys-21. The hydrolysis of VIP at Arg-14 was slightly affected by the presence of the dansyl group at the N-terminus. While the Km value was unaffected, the kcat value decreased, yielding a kcat/Km ratio that was eightfold lower. The addition of calcium chloride to the reaction mixture resulted in a slight decrease in the kcat/Km ratio. Cleavage of dansyl-VIP by tryptase was completely inhibited by DesPro2-Arg15-Aprotinin.
Automation↗
Central neurocytoma: clinical, immunohistologic, and biologic findings of a human neuroglial progenitor tumor.
BACKGROUND: Central neurocytomas are rare brain tumors recognized by their typical radiologic and histologic features. In general, a good prognosis is achieved by total removal. The histogenesis is still under debate, but a neuronal origin is widely assumed. METHODS: This study presents the clinical and immunohistologic findings of five patients and the results of cell culture experiments of two patients with central neurocytoma treated surgically between 1983 and 1993. RESULTS: The patient age at diagnosis ranged from 21 to 30 years (mean, 25 years). The male-to-female ration was 1:4. Raised intracranial pressure due to hydrocephalus was the main cause of the clinical manifestations. Total resection was achieved in two cases. Four patients received radiotherapy. One patient suffered a recurrence 1 year after surgery, requiring a second resection and radiotherapy. Follow-up studies took place between 1 and 10.5 years (mean, 7.1 years). To date, all patients are free of their tumors. Two patients suffered from permanent memory disturbances after surgery. Immunohistochemistry confirmed the neuronal nature of the tumors. Cell-culture studies, which have been carried out for the first time, demonstrated concomitant expression of neuronal (synaptophysin) and glial (GFAP) markers. CONCLUSION: Total removal is the therapy of choice. In tumor recurrence or limited surgery (e.g. due to severe affliction of the fornical structures), radiotherapy has shown to be efficacious. The cell-culture experiments give new insight on the histogenesis of central neurocytoma, indicating that the tumor arises from an undifferentiated precursor cell with the capacity of bipotential neuroglial differentiation.
Adult↗