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Biomedical subjects

M Gilbert

Publications and source records attributed to M Gilbert.

287 records · Page 16Linked to original sources
PubMedDate not supplied

Halogenated general anesthetics in visual photoreceptor membranes as examined by static and dynamic properties of rhodopsin.

The visual pigment rhodopsin was used as an intrinsic probe to measure the effect of incorporation of enflurane into bovine rod outer segment disk membranes. At moderately low enflurane concentration, we find that, while extrinsic probes show little membrane perturbation, rhodopsin may experience large changes with respect to the native lipid-protein interactions which modulate some of its properties. Enflurane induces a small blue shift in the pigment lambda max and a strong inhomogeneity in its photochemical behavior. As a function of enflurane concentration, there appears to be an increasing population of rhodopsin molecules for which the metarhodopsin I-->II transition is blocked, while it is accelerated in the remaining population. Under these conditions, electrophoresis and partial membrane solubilization indicate that an increasing amount of rhodopsin does not behave like a free monomeric species. These results are all consistent with a reduction of the membrane order accompanied by lateral aggregation of rhodopsin in the presence of enflurane. By comparison with the perturbation probed by a spin label, the large molecular environment change experienced by the rhodopsin molecule suggests that enflurane may concentrate at the lipid-protein interface.

Animals↗
PubMedDate not supplied

Stimulation of transcriptional regulatory activity by substance P.

The neuropeptide substance P (SP) is one of the principal mediators of neurogenic inflammation as well as a neurotransmitter in nociceptive affect neurons. The mechanisms by which binding of SP to its receptor stimulates diverse downstream biologic effects remain unknown. In order to elucidate this process we have established stably transfected cell lines expressing functional rat SP receptors (KNRK-SPR). When stimulated by SP, KNRK-SPR cells respond by simultaneously mobilizing intracellular Ca2+ and increasing cAMP levels. To determine if SP stimulation activates downstream transcriptional regulatory factors, we transfected KNRK-SPR cells with plasmids containing the activator protein 1 (AP-1) and cAMP-responsive (CRE) enhancer elements coupled to the chloramphenicol acetyltransferase (CAT) reporter gene. Stimulation with SP 1-1,000 nM caused a 1.5- to 2-fold increase in CAT activity in both AP-1-CAT- and CRE-CAT-transfected KNRK-SPR cells. Northern and Western blot analyses demonstrate that the mechanism by which SP stimulates AP-1 enhancer activity involves increases in both c-jun mRNA and protein. Moreover, gel retardation assays with oligomers containing the AP-1 and CRE binding sites showed that SP induces specific retardation bands consistent with increases in AP-1 and CRE complexes. These experiments suggest that SP-mediated stimulation of cells involves the participation of two signaling pathways resulting in several transcriptional regulatory mechanisms being activated.

Animals↗
PubMedDate not supplied

Microbial growth patterns in a total parenteral nutrition formulation containing lipid emulsion.

Microbial growth of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans was evaluated in a standard amino acid-dextrose-based total parenteral nutrition (TPN) solution, 10% lipid emulsion, and a combined TPN formulation containing amino acids, dextrose, and lipid emulsion. At an initial inoculum of 10(4) CFU/ml, all three bacterial organisms grew well in 10% lipid emulsion, died in the standard solution and grew only minimally or died in the combined formulation. C. albicans grew in all three formulations at an initial inoculum of 10(4) CFU/ml; however, at an initial inoculum of 10(2) CFU/ml, which approximates touch contamination, growth of Candida in the standard and combined formulations was less than 1 log at 24 hr in contrast to the 10% lipid emulsion which showed significant growth greater than 2 log at 24 hr. It is concluded that a 24-hr infusion time is safe for the combined TPN formulation used in this study. This should result in significant cost savings compared to the previously recommended 12-hr infusion time.

Bacteria↗
PubMedDate not supplied

Temporal and spatial regulation of the expression of BAD2, a MAP kinase phosphatase, during seizure, kindling, and long-term potentiation.

Recent studies indicate that stimulation of NMDA receptors in cultured hippocampal cells activates MAP kinase. Although the pathway whereby MAP kinase is activated has been been characterized, little is known about the mechanisms that shut off MAP kinase. In the course of analyzing several immediate-early genes identified previously by differential screen as inducible by seizure activity, we found that one of them, BAD2, encodes dual purpose, threonine/tyrosine phosphates with specific activity directed against MAP kinase (MKP-1). In situ hybridization of BAD2 demonstrates that stimuli that produce seizure, kindling, and long-term potentiation cause a rapid increase in BAD2 mRNA (within 0.5-1 hr after stimulation) that has, in each case, a distinctive pattern of expression in the brain. In these regions, the induction of a MAP kinase-specific phosphatase may provide a negative feedback control associated with long-term synaptic changes.

Amino Acid Sequence↗
PubMedDate not supplied

Correlation of tumor p53 and PCNA with response and survival of glioblastoma in patients treated with an ECOG protocol of pre-irradiation chemotherapy.

BACKGROUND: The ability to predict treatment responsiveness and survival of patients with glioblastoma multiforme, the most malignant and most common primary brain tumor, would be a valuable asset. Tumor and proliferation markers such as p53 and PCNA have been immunohistochemically defined and have been useful in other tumors in determining prognosis. Therefore, the authors studied the correlation of responsiveness to treatment, time to progression and survival with p53 and PCNA labeling indices in a pre-irradiation chemotherapy study of the glioblastoma multiforme. METHODS: Immunohistopathology for labeling indices for p53 and PCNA using formalin-fixed, paraffin-embedded tissue from the glioblastomas of 23 patients entered into a phase II ECOG trial of pre-irradiation chemotherapy were defined using the streptavidin-peroxidase technique with AEC chromogen. The labeling indices were correlated with response to treatment time to progression and overall survival. Most patients received three cycles of BCNU for three days over three months and cisplatin monthly for three days over three months prior to external beam irradiation. RESULTS: There were no significant differences in treatment response, time to progression or overall survival in glioblastoma, patients with positive p53 labeling index (> 5%) versus a negative p53 labeling index (< or = 5%) or positive PCNA labeling (> 10%) versus a negative labeling index (< or = 10%) or any combination of P53 and PCNA labeling indices. CONCLUSIONS: Using this protocol of pre-irradiation chemotherapy, p53 and PCNA labeling indices in the glioblastoma multiforme did not predict treatment benefit.

Adult↗
PubMedDate not supplied

Determining the relationship between end-of-life decisions expressed in advance directives and resuscitation efforts during cardiopulmonary resuscitation.

In recent years, there has been an increased focus on end-of-life decisions and the use of medical technology. It is not well documented in the literature whether or not and to what extent patients' advance directives are used for directing resuscitative efforts. The purpose of this study was to determine how useful patients' advance directives were to members of the health care team in determining treatment and end-of-life decisions among patients who received cardiopulmonary resuscitation (CPR) efforts. Medical records of 135 adult patients who had undergone CPR efforts within the previous year were reviewed to determine if and to what extent advance directives were useful in directing end-of-life care and treatment decisions. Only 35 of these patients had advance directives. Three categories for advance directives emerged: those that were "independently directive," those that were "vague and required further clarification," and those that were "nondirective." Information from this study may be used to clarify treatment options for end-of-life care and to determine if and what further interventions are required to ensure that advance directives can be executed as meaningful documents.

Advance Directive Adherence↗
PubMedDate not supplied

[White thrombus syndrome. Apropos of 4 new cases].

Four new cases of the white thrombus syndrome have been treated over the last 3 years. This is a rare but serious complication of heparin therapy, multifocal arterial thrombi developing in all three patients without signs of a hemorrhagic syndrome due to the thrombopenia. Physiopathologic mechanisms of this immunity phenomenon are discussed. The diagnosis should be evoked in all patients receiving heparin who on about the 10th day present vascular manifestations of the thrombosis type, rarely in association with a hemorrhage. Blood platelet levels are reduced to below 5000/mm3. Confirmation of diagnosis is by positive results of hematologic and immunologic tests. Treatment involves immediate cessation of heparin and administration of anti-platelet aggregation agents and anti-vitamins K or low molecular weight heparin, combined with arterial thrombectomy or prevention of pulmonary emboli.

Aged↗
PubMedDate not supplied

Direct detection of idiotypic determinants on blotted monoclonal antibodies.

The protein-blotting technique has been tested as a mean to study the expression of idiotypic determinants. A monoclonal BALB/c antipoly (Glu60-Ala30-Tyr10) GAT antibody (G5) was caused to migrate on SDS gel and transferred to a nitrocellulose filter. To facilitate the renaturation of the idiotypic determinants, the blotted proteins were incubated in NP40 buffer, immediately after the transfer. The ability of two anti-idiotypic sera to detect two defined idiotypic specificities of the blotted G5 molecules was investigated. When G5 was electrophoresed on SDS gel under non-reducing conditions, a specific detection of two idiotypic specificities of the G5-blotted molecules was obtained. On the other hand, when G5 was migrated under reducing conditions, none of the two antiidiotypic sera gave a staining of the heavy and the light chains. This result indicates that molecules expressing conformational idiotypic determinants can be detected by protein-blotting technique after migration on SDS gel. Moreover, this suggests the possible interest of this technique to analyse non-antibody molecules bearing idiotypic determinants.

Animals↗
PubMedDate not supplied

[Problems in detection of mycoplasma contamination in cell cultures (author's transl)].

A total of 135 cell lines was examined for mycoplasma contamination using two techniques: isolation and specific DNA-staining with DAPI or "Hoechst 33258". The two techniques showed similar results in 64% of the cases of cell contamination while the remainder was detected only by one or the other techniques: 12,82% by the staining technique and 23% by the isolation technique, which shows that the 2 techniques are complementary. The staining technique is very quick, easy to execute, very sensitive, and should be the method of choice to detect contamination when the mycoplasma do not grow in acellular media.

Animals↗
PubMedDate not supplied

Evolution of a role to enhance care coordination.

The recent trend toward shorter hospital stays has prompted health care personnel in acute care settings to reevaluate models of coordinating patient care. In whatever model is adopted, there must be someone whose role is to focus on achieving quality patient outcomes in a shorter time frame. Our institution has piloted several different models with various job classes to fulfill the role. However, the primary focus of the models-to enhance care coordination-remained unchanged. The initial care coordination model was the development of patient care coordinator role by converting the charge nurse position on the unit. The second model our institution developed occurred during a management restructuring. This model created a new position, a nursing practice coordinator, who had previously been a management support person with supervisory responsibilities. We now envision the role to be assumed by a nurse practitioner. The nurse practitioner's broader scope of practice potentially can further enhance coordination of care. In this article, the authors describe the development process, issues and interventions, and lessons learned during each step of redesigning a case management model.

Case Management↗