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At least 721 records · Page 40Linked to original sources
PubMed1976

Combination chemotherapy of adult acute lymphocytic leukemia.

Seventeen adults with previously untreated acute lymphocytic leukemia (ALL) received thioguanine, vincristine, dexamethasone, and pyrimethamine for remission induction. Nine patients (53%) achieved complete and 5 (30%) partial remissions. Once in complete remission patients were given two closely separated consolidation courses followed by monthly maintenance courses of the same regimen with the addition of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) every other month during maintenance therapy. The median duration of complete remission was 176 days (range 38 to 605). The median survival for all patients was 405 days (range 30 to 1,058+). Oral pyrimethamine and CCNU were used for their potential activity as prophylactics against meningeal leukemia. Dexamethasone was used instead of prednisone because of the potential enhancement of granulocyte mobilization by the former. Six patients (35%) developed meningeal leukemia while on initial induction or maintenance therapy, 5 within 6 months of diagnosis. Life-threatening infections occured in 10 patients (59%) during induction. Whereas the regimen effectively induced complete remission in about half of previously untreated adults with ALL, it was not effective in maintenance. The incidence of meningeal leukemia and infection during induction was high. Oral pyrimethamine was inadequate prophylaxis for meningeal leukemia; dexamethasone did not reduce the incidence of serious infection.

Adolescent↗
PubMedDate not supplied

Histomorphometric analysis of intraoral split-thickness skin grafts.

Transposition of split-thickness skin grafts from the anterior thigh to the oral cavity is an ideal method for reconstruction of selected defects following major oncologic ablative surgery. This alternative potentially allows for tongue mobility, deglutition, and articulation superior to that obtained with bulky adynamic myocutaneous flaps. We have examined the adaptive responses of split-thickness skin grafts to the intraoral environment with biopsies from 10 patients 11 to 90 months following oral cavity reconstruction. Histologic examination of intraoral skin grafts shows preservation of the cytoarchitecture of the epidermis, an absence or atrophy of skin appendages, and a statistically significant thinning of the keratin layer. A "junctional zone" between the normal oral cavity mucosa and the skin graft was identified. This zone is characterized by an abrupt transition from keratinized stratified squamous epithelium with a prominent granular layer, to nonkeratinized stratified squamous epithelium lacking a granular layer. This study clearly demonstrates that split-thickness skin, when transposed to the oral cavity, maintains the epidermal phenotype and does not assume the histologic characteristics of mucosa.

Aged↗
PubMed1995

Associations between the neuroendocrine and immune systems.

Organisms respond to infection with complex adaptations involving bidirectional communication between the immune and neuroendocrine systems. The idea of intercellular communication between the neuroendocrine and immune systems via common signal molecules has provided a conceptual framework for such crosstalk. The studies to date show that cells of the immune system contain receptors for neuroendocrine hormones and can also be considered a source of pituitary and hypothalamic peptides. The structure and pattern of synthesis of these peptides by leukocytes appear similar to neuroendocrine hormones, although some differences exist. Once secreted, these peptide hormones may function as endogenous regulators of the immune system as well as conveyors of information from the immune to the neuroendocrine system. The plasma hormone concentrations contributed by lymphocytes usually do not reach the levels required when the pituitary gland is the source, but because immune cells are mobile, they have the potential to locally deposit the hormone at the target site. Likewise, other studies show that cells of the neuroendocrine system contain receptors for cytokines and can also be considered a source of cytokines, particularly interleukin-1 (IL-1) and IL-6. In the pituitary IL-1 beta coexists with thyroid stimulating hormone in a subpopulation of thyrotropes, suggesting it may have a role as a pituitary paracrine factor. The cytokines, including IL-1, IL-2, IL-6, interferon-gamma, and tumor necrosis factor, exert profound effects on hypothalamic pituitary axes. It is our hypothesis that the relay of information to the neuroendocrine system represents a sensory function for the immune system wherein leukocytes recognize stimuli that are not recognizable by the central and peripheral nervous systems (i.e., bacteria, tumors, viruses, and antigens). The recognition of such noncognitive stimuli by immunocytes is then converted into information and a physiological change occurs. Future studies into the physiological role that cytokines and neuroendocrine hormones have in these systems will be of considerable interest for both immunologists and endocrinologists.

Animals↗
PubMed1987

Determination of 7-piperidino-1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-one (DN-9693) in human plasma and urine by high-performance liquid chromatography with electrochemical detection: application to studies on disposition of DN-9693 in healthy human volunteers.

A procedure for the determination of a newly developed antiadhesive agent, 7-piperidino-1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-on e (DN-9693; 1), in human plasma and urine at low nanogram levels by high-performance liquid chromatography with electrochemical detection is described. Plasma and urine samples were made alkaline with 1 M KOH solution and extracted with chloroform. After removing organic solvent, the extracts reconstituted in methanol were applied to a reversed-phase octadesyl-packed column and eluted with a methanol: phosphate buffer (pH 8.0) mobile phase. The applied potentials were set at 0.80 and 0.95 V versus a silver-silver chloride reference electrode for the analyses of plasma and urine specimens, respectively. The method provides a recovery of greater than 90% and a within-day precision of less than 5%. The minimum quantifiable levels for 1 in plasma and urine using 1 mL of sample are 1 and 4 ng/mL, respectively. The method has been successfully used for the determination of 1 in plasma and urine samples from healthy human volunteers after intravenous infusion of the drug.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

Natural occurrence of 2'-phospho-cyclic ADP ribose in mammalian tissues.

2'-Phospho-cyclic ADP-ribose (P-cADPR) is a newly identified Ca2+-mobilizing agent derived from NADP that stimulates intracellular Ca2+ release by a mechanism distinct from inositol 1, 4, 5-trisphosphate. In this report, we show that P-cADPR is an endogenous metabolite in bovine tissues with basal levels ranging from 17.6 to 89.5 fmol/mg protein. The natural occurrence of this Ca2+-mobilizing nucleotide provides a potential link between NADP(H) metabolism and regulation of Ca2+ homeostasis.

Adenosine Diphosphate Ribose↗
PubMed2005

Population dynamics of RNA viruses: the essential contribution of mutant spectra.

Cells and their viral and cellular parasites are genetically highly diverse, and their genomes contain signs of past and present variation and mobility. The great adaptive potential of viruses, conferred on them by high mutation rates and quasispecies dynamics, demands new strategies for viral disease prevention and control. This necessitates a more detailed knowledge of viral population structure and dynamics. Here we review studies with the important animal pathogen Foot-and-mouth disease virus (FMDV) that document modulating effects of the mutant spectra that compose viral populations. As a consequence of interactions within mutant spectra, enhanced mutagenesis may lead to viral extinction, and this is currently investigated as a new antiviral strategy, termed virus entry into error catastrophe.

Animals↗
PubMed1985

Psychosomatic symptoms, stress, and modernization: a model.

The quantity of research on the effects of stress on disease has increased substantially in recent years, but little effort has been devoted to examining the effects of cultural influences in the stress process. A model is proposed in this paper in which cultural context exerts a modifying influence on the relationship between sociocultural stressors and psychosomatic symptoms, specifically in the context of modernization. In change situations involving increasing modernization there is increased differentiation in systems of social stratification within a community, due to increased potential for upward social mobility. The individuals who are upwardly mobile adopt a particular style of life, involving the acquisition of western consumer goods, as symbolic of their success. Lower class individuals strive to attain this same style of life as a claim to a higher status social identity, but their lower economic condition results in stressful incongruities and higher psychosomatic symptoms. Individuals who are successful in upward mobility are confronted by a different set of stressors that are primarily intrapsychic in nature. Events and circumstances perceived as threats to their self-identity are related to more psychosomatic symptoms. Thus, the meaning of specific stressors changes depending on the sociocultural context of the individual, and this meaning serves as a bridge between environmental circumstances and physiological outcomes. This model receives substantial empirical support in two field studies. Limitations of the model and implications for future research are discussed.

Adaptation, Psychological↗
PubMed2005

[Effectiveness of a multifactorial intervention to reduce physical restraints in nursing home residents with dementia].

At present, observational studies and expert opinion are the best evidence for the use of physical restraints. Large regional and national disparities are described in acute and long-term care. Epidemiological data demonstrate a prevalence of 3-5% body-fixed or near body restraint devices. The hip fracture rate in Germany are approximately 50 per 1000 resident years. Between 40-50% of the residents in nursing homes are treated with psycho-tropic medication potentially limiting their physical mobility. The presented study protocol was designed to test the effectiveness of a multifactorial intervention to reduce physical restraints in long-term care (LTC) residents particularly with cognitive impairment. The intervention consists of an educational and an organizational part to empower staff members to improve their skills and practice in using restraints. Technical devices to reduce fall related injuries are additionally offered to the LTC facilities. The study population includes 200 LTC residents in 54 facilities in three states in Germany. The sample size calculation was based upon a 5% prevalence rate in the control group and an expected reduction of 50% in the intervention group. The protocol is a waiting-list control design. All waiting facilities will be offered to participate after their waiting period. Primary endpoints are the number of restrained residents and resident time (hours) of being restrained. The use of psychotropics, falls, fall-related injuries and the incidence of residents newly being restrained is being monitored. The study starts with a baseline documentation of all facilities followed by randomization and a three month intervention. Change agents will be responsible for the intervention. Technical devices will include a newly developed soft hip protector and sensor mats which notice the intent of leaving the bed. The aim of the study is to develop an evidence-based model for a knowledge transfer project to implement minimum restraint environments in LTC.

Accidental Falls↗
PubMed2006

A still image of a transient rash captured by a mobile phone.

The diagnosis of adult onset Still's disease (AOSD) can be difficult as the differential diagnosis is broad, it is based on clinical criteria and the signs, for example rash, can be transient. Clinical photography has an obvious role, and with modern technology, is now in the hands of physicians. We report a case of AOSD where an image of a transient rash taken with a camera phone allowed the diagnosis to be established. Further, we discuss the controversies around hospital bans on mobile phones (due to potential incompatibility with medical devices) and the reality of their widespread use. We conclude that, providing safeguards of consent and data storage are in place, the camera phone is a useful tool in rheumatology practice.

Adult↗
PubMed1988

Calcium mobilization by angiotensin II and neurotransmitter receptors expressed in Xenopus laevis oocytes.

Specific receptors for angiotensin II (AII) were expressed in albino Xenopus laevis oocytes co-injected with poly(A)+ mRNA isolated from rat adrenal cortex and the calcium-specific photoprotein, aequorin. In such oocytes, AII elicited rapid, dose-dependent rises in cytosolic free calcium with light emission responses up to 100-fold above basal levels. Ligand-induced light emission was also observed in oocytes injected with rat brain mRNA and stimulated with acetylcholine and glutamate. These findings demonstrate that mammalian AII receptors expressed in Xenopus oocytes are functionally linked to intracellular Ca2+ mobilization, and indicate the potential value of aequorin-injected oocytes for rapid and specific screening of mRNAs transcribed from expression libraries containing cloned receptor cDNAs.

Acetylcholine↗
PubMed1995

Capillary zone electrophoretic resolution of recombinant human bone morphogenetic protein 2 glycoforms. An investigation into the separation mechanisms for an exquisite separation.

Recombinant human bone morphogenetic protein 2 (rhBMP-2) is a disulfide-linked homodimeric glycoprotein (M(r) = 30,000) which induces bone formation in vivo in several animal model systems. In this paper, we report the separation of a homogeneous rhBMP-2 sample into nine peaks by capillary zone electrophoresis (CZE), using a simple, pH 2.5, phosphate buffer containing no additives. The nine peaks have been identified to be glycoforms of rhBMP-2 [designated as (rhBMP-2)2-(GlcNAc)4(ManZ), where Z varies from 10 to 18]. The difference between any adjacent pair of peaks is only one mannose residue (M(r) = 162). The ability of CZE to resolve rhBMP-2 glycoforms having the same charge and differing only 0.5% in molecular mass, without resorting to chemical complexation, is both unexpected and intriguing. Possible mechanisms explaining how the additional mannose can affect the mobility of rhBMP-2 glycoforms were explored. Zeta potentials of various glycoforms were calculated from their mobilities and interpreted in light of diffuse double layer parameters. Our results suggest that CZE employing a low-pH buffer, where proteins are highly charged, may be uniquely suitable for complex protein glycoform analysis.

Amino Acid Sequence↗
PubMed1991

Activation of class II gene transcription by regulatory factors is potentiated by a novel activity.

A novel activity (USA) stimulated activator-dependent transcription in a reconstituted system in conjunction with natural TFIID, resulting in 10- to 50-fold levels of induction by regulatory factors. USA mediated a modest induction by USF in conjunction with either recombinant human TFIID, intact yeast TFIID, or the evolutionarily conserved C-terminal portion of yeast TFIID. Upon further purification, USA was resolved into two components that had opposite effects on core promoter activity and that in combination potentiated activator function. Gel mobility shift experiments indicated physical interactions between the inhibitory activity and TFIID, suggesting that the additional components (cofactors) associate with the preinitiation complex both to reduce promoter activity in the absence and to increase promoter activity in the presence of transcriptional activators.

Adenoviruses, Human↗
PubMed1987

Effects of TMB-8 and dantrolene on ACTH- and angiotensin-induced steroidogenesis by frog interrenal gland: evidence for a role of intracellular calcium in angiotensin action.

The influence of intracellular calcium on the steroidogenic response of adrenocortical tissue to ACTH and angiotensin has been studied in the frog, using a perifusion system technique. The release of corticosterone, aldosterone and prostaglandins in the effluent medium was monitored by specific radioimmunoassays. TMB-8 and dantrolene, two potential blockers of calcium mobilization from intracellular pool(s), were tested. Dantrolene (5 X 10(-5) M) significantly reduced basal and angiotensin-induced corticosterone and aldosterone production but had little effect on ACTH-evoked steroid release. Conversely TMB-8 (10(-4) M) profoundly depressed spontaneous as well as ACTH- and angiotensin II-induced corticosteroid secretion, suggesting that this compound may affect not only calcium mobilization from the endoplasmic reticulum pool but also calcium influx. Adrenal glands perifused with both dantrolene and calcium-free medium showed no response to angiotensin II. Conversely, in calcium-free conditions and in the presence of dantrolene, angiotensin II still caused an increase in prostaglandin synthesis. Taken together, these results indicate that 1) dantrolene is a more specific agent than TMB-8 in inhibiting calcium mobilization from intracellular pool(s); 2) ACTH increases corticosteroidogenesis without inducing mobilization of intracellular calcium; 3) angiotensin II stimulates both the efflux of calcium from the endoplasmic reticulum and the influx of calcium through the plasma membrane; 4) calcium is required after prostaglandin production in the steroidogenic response of frog interrenal gland to angiotensin II.

Adrenal Cortex Hormones↗
PubMed1984

A study of triiodothyronine-catecholamine interactions: their effect on plasma fatty acids in Pacific hagfish Eptatretus stouti.

Plasma circulating levels of fatty acids (PFA) were measured in intact and in triiodothyronine (T3)-treated Pacific hagfish Eptatretus stouti. Intraperitoneal injection of both pharmacological (200 ng/g) and physiological (1 ng/g) doses of T3 caused an elevation of PFA 24 and 48 hr after treatment. The implantation of capsules containing the antithyroid compound, 6-propylthiouracil (6-PTU) decreased PFA levels. Twenty-four hr after T3-injection the norepinephrine (NE) content of plasma declined, whereas epinephrine (E) titres increased. Forty-eight hr after T3-treatment the mean titres of dopamine (D) and NE were lower than in the control group of hagfish. The treatment of hagfish with E in either pharmacological (2-3 micrograms/g) or physiological (2-3 ng/g) doses did not cause any elevation of PFA during the 72 hr following injection. In the same experiment the high dose of E induced long-lasting hyperglycemia, whereas the low dose had no substantial effect on glycemic levels. The data provide evidence that in hagfish, unlike in higher animals, the observed lipolytic effect of administered T3 is not mediated through the potentiation of the fat mobilizing action of catecholamines.

Animals↗
PubMed1996

Monte Carlo studies on potentiometric titration of (carboxymethyl)cellulose.

Monte Carlo simulations of the potentiometric titration are carried out for (carboxymethyl)cellulose in aqueous salt solutions by a previously developed method. A nearly elliptic cylinder with spherical ionizable groups is assumed as model of (carboxymethyl)cellulose molecule. The spherical charges with a hard core potential are adopted as mobile hydrated ions. A fairly satisfactory agreement of the titration curves with the experimental data is achieved by using reasonable molecular dimensions. Dependence of the calculated titration profiles on the molecular model and the characteristics of the system are discussed.

Journal Article↗
PubMed1988

A cautionary note on the use of blot hybridization for RNA size determination.

The ease with which RNA blot hybridization analysis can be performed makes it among the most widely used analytical tools in molecular biology. Hybridization with a labeled probe, subsequent to size fractionation and immobilization on a filter, allows one to approximate both the size and abundance of a given RNA in a single experiment. This communication demonstrates that dramatic differences in the electrophoretic mobility of the yeast GCN2 transcript are observed when size fractionation on formaldehyde gels is compared to fractionation of glyoxalated RNA. Both routinely used systems are considered to be fully denaturing. The anomalous mobilities therefore pose a potential problem when size determination is performed using a single gel system.

Blotting, Northern↗
PubMed1995

A new mobilizable cosmid vector for use in Vibrio cholerae and other gram-negative bacteria.

A new mobilizable cosmid vector, pCOS5, was engineered for use in Vibrio cholerae (Vc). Plasmid pCOS5 is small in size (7286 bp), contains the oriT from plasmid RK2, and has several unique restriction sites. The complete nucleotide sequence of pCOS5 was deduced from the DNA fragments used in its construction. Biparental matings using Escherichia coli (Ec) SM10 and triparental matings using Ec DH5 alpha[pRK2013] were used to measure the conjugation frequency of pCOS5 and pAJM1, a clone containing a 40-kb insert of chromosomal DNA from Vc ligated into pCOS5. Transfer of pCOS5 or pAJM1 to Vc occurred at a frequency of between 10(-2)-10(-3) transconjugants per recipient cell. The promiscuous nature of RP4/RK2 transfer functions makes pCOS5 a potentially useful vector for mobilizing large fragments of cloned DNA between different Gram- bacteria that support replication of ColE1 plasmids or as a mobilizable suicide vector in Gram- bacteria where replication of ColE1 plasmids is not supported.

Base Sequence↗
PubMed1987

Analysis of gossypol by high performance liquid chromatography.

Several high performance liquid chromatographic methods for the analysis of gossypol in different kinds of sample were developed. (1) Pure gossypol: separation on C18 column with MeOH/H2O/CHCl3 (70:30:40) containing 0.1% H3PO4 as mobile phase or on SO3H column with MeOH/citrate buffer (pH 6.3) (55:45) as mobile phase was recommended. With these systems, minute amounts of contaminants difficult to separate by other HPLC systems could be determined. (2) Plant material: acetone was selected as the extraction solvent. After evaporation of acetone from the extract, the residue was redissolved in 1% HOAc in CHCl3. An aliquot of this solution was chromatographed and quantified by peak area method. The mean recovery of pure gossypol added to plant material was 91.1 +/- 1.1% (S.D.). (3) Plasma sample: a HPLC method with electrochemical detector was developed. A plasma sample with glutathione as protective agent and gossypol dimethyl ether as internal standard was introduced on to a C18 pre-column. By using column-switching technique, a certain part of the eluate containing gossypol and gossypol dimethyl ether was subjected to a C8 analytical column for further separation. MeOH/citrate buffer (pH 3.2) (80:20) was used as the mobile phase. The optimum potential for detection was +0.6 V vs. Ag-AgCl. The assay sensitivity was 5 ng/ml. This method is sensitive and selective, suitable for clinical pharmacokinetic studies.

Chromatography, High Pressure Liquid↗