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Biomedical subjects

R Kramer

Publications and source records attributed to R Kramer.

At least 55 records · Page 3Linked to original sources
PubMed1993

Alpha 6 integrin is up-regulated in step increments accompanying neoplastic transformation and tumorigenic conversion of human fibroblasts.

Integrins are a family of transmembrane glycoproteins that serve as cell-cell and cell-substratum adhesion molecules and help regulate cellular differentiation and proliferation. In malignant cells, which exhibit abnormal differentiation and growth properties, the expression of an altered integrin repertoire could therefore be expected. From a tumorigenic human fibrosarcoma cell line we isolated a unique complementary DNA corresponding to the alpha 6 integrin subunit. Northern blot analysis using this complementary DNA as probe indicated that alpha 6 integrin mRNA was abundantly expressed in all neoplastically transformed fibroblast cell lines but not in normal diploid fibroblasts. In addition to its potential as a marker for the neoplastic transformation of human fibroblasts, the alpha 6 integrin mRNA was also found to be consistently expressed at higher levels in tumorigenic fibroblasts than in immortalized but nontumorigenic fibroblasts. This differential expression of alpha 6 integrin was reflected at the cell surface protein level using cytofluorometric analysis with specific monoclonal antibody. In contrast, the levels of cell surface expression of other integrins were unchanged (such as alpha 3 and beta 1) or down-regulated (such as alpha 5) when transformed cells were compared with normal fibroblasts. The incremental up-regulation of alpha 6 integrin was selective and paralleled the progression of normal cells to immortalized cells and finally to tumorigenic cells. This elevated alpha 6 subunit associated with the beta 1 subunit to form a heterodimer receptor for laminin. Since fibrosarcoma cell invasion of basement membrane has been shown to involve alpha 6 beta 1 integrin, then the induction or up-regulation of alpha 6 expression is an important step in tumor progression and evolution to the invasive phenotype in fibrosarcoma.

Animals↗
PubMed1993

Self-recognition in helicate self-assembly: spontaneous formation of helical metal complexes from mixtures of ligands and metal ions.

On treatment with copper(I) ions, mixtures of the [oligo(2,2')-bipyridine] strands 2-5 yield spontaneously the double helicates 2H(2)-2H(5) without significant crossover. Similarly, when a mixture of the two tris-bypyridine ligands 1 and 3a (containing different substitutions) is allowed to react with copper(I) and nickel(II) ions, only the double helicate 2H(3a) and the triple helicate 3H(1) are formed. Thus, these systems undergo self-assembly of helicates with self-recognition. The process represents a self/nonself-discrimination involving the preferential binding of like metal ions by like ligand strands in a mixture to selectively assemble into the corresponding helicates. In a broader perspective, these results point to a change in paradigm from pure compounds to instructed mixtures--that is from seeking chemical purity to designing programmed systems composed of mixtures of instructed components capable of spontaneously forming well--defined superstructures through self-processes.

Journal Article↗
PubMed1993

Modulation of mdr-1 expression by a H-ras oncogene in a human colon carcinoma cell line.

In an established colon differentiation model, introduction of a c-H-ras-1 oncogene into a poorly differentiated human colon carcinoma cell line (Clone A) results in changes associated with the acquisition of a more differentiated phenotype. Down-regulation of mdr-1 mRNA was shown to accompany ras-related differentiation events resulting in decreased Pgp synthesis and a significant reduction in membrane Pgp as detected by immunoprecipitation, Western-blot and FACS analysis. Consistent with these observations was a reduction in Pgp-mediated drug resistance associated with Clone-A ras transfectants, with no alteration in drug sensitivity being observed with non-MDR drugs in these cells. An alternative differentiation model involves exposure of Clone-A cells to sodium butyrate. Under these conditions, differentiation-related changes resulted in up-regulation of mdr-1 mRNA and Pgp synthesis, although no alteration in drug sensitivity was recorded. In agreement with this observation, the levels of membrane-associated Pgp remained unchanged throughout the period of exposure to sodium butyrate. This study shows that modulation of Pgp expression in colon differentiation is dependent upon the differentiation induction agent used.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

The multidrug resistance (mdr1) gene product functions as an ATP channel.

The multidrug resistance (mdr1) gene product, P-glycoprotein, is responsible for the ATP-dependent extrusion of a variety of compounds, including chemotherapeutic drugs, from cells. The data presented here show that cells with increased levels of the P-glycoprotein release ATP to the medium in proportion to the concentration of the protein in their plasma membrane. Furthermore, measurements of whole-cell and single-channel currents with patch-clamp electrodes indicate that the P-glycoprotein serves as an ATP-conducting channel in the plasma membrane. These findings suggest an unusual role for the P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Constitutive expression of multidrug resistance in human colorectal tumours and cell lines.

In this study we report detection of mdr1 gene expression in the liver metastases of 7/11 patients with colon carcinoma and characterise the MDR phenotype associated with a panel of 19 human colon carcinoma cell lines. Within this panel, mdr1 mRNA biosynthesis and surface localisation of Pgp were assessed with respect to MDR functionality where the cell lines are representative of different clinical stages of tumour progression, metastatic potential and differentiation. The data indicates that constitutive levels of mdr1 mRNA/Pgp expression may not necessarily result in the functional expression of the MDR phenotype. While low levels of mdr1 mRNA/Pgp were detected in 5/8 well differentiated colon cell lines, only 2/8 were functionally MDR. In contrast, 10/11 moderate and poorly differentiated lines expressed mdr1 mRNA/Pgp and of these, 9/11 were functionally MDR. The phosphorylation status of the mature 170 kD P-glycoprotein and the surface localisation of this glycoprotein showed the strongest correlation with functionality. Analysis of cell lines for cross-resistance and chemosensitivity profiles against a battery of chemotherapeutic drugs suggests multiple mechanisms, in addition to Pgp, contribute to the overall resistance of colorectal cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

A Delphi study of pediatric oncology nurses' facilitative behaviors.

Using a classic Delphi methodology, this study identified the nursing behaviors and interventions that oncology nurses rated as most important in facilitating the patient's, parents', and siblings' coping efforts with the effects of disease and treatment. Random selection of 300 pediatric oncology nurses resulted in a final sample of 69 nurses who completed all 3 rounds of the Delphi. The majority of the nurses were younger than 35 years of age, had less than 10 years of experience, were educated with at least a bachelor's degree, and practiced in an all-oncology setting. Twenty-eight facilitative behaviors were identified for the child with cancer, 25 for the parents, and 25 for the siblings. Results of this study support previous research on patient, parent, and sibling coping.

Adaptation, Psychological↗
PubMed1993

The effect of pulmonary impairment on all-cause mortality in a national cohort.

The association between pulmonary impairment and all-cause mortality was investigated among white subjects in a follow-up study of a large national cohort. Pulmonary function was measured during the National Health and Nutrition Examination Survey (NHANESI) (1971 to 1975); subsequent mortality information was obtained from the 1987 NHANES I Epidemiologic Follow-up Study (1982 to 1987). Of 4,764 white sample persons, ages 25 to 74 years examined during NHANES I, 658 (13.8 percent) were identified as having pulmonary impairment defined as a FEV1/FVC < or = 69 percent. A total of 743 (15.6 percent) sample persons died during the follow-up period. The association between pulmonary impairment and all-cause mortality was examined for male and female subjects separately using the Cox proportional hazards model controlling for age, smoking, educational level, body mass index, and respiratory diseases. The analysis suggests that reduced FEV1 percent predicted was a significant risk factor for mortality among both sexes, and the FEV1/FVC ratio was significantly associated with all-cause mortality among male subjects only.

Adult↗
PubMed1992

Evaluation of the antihypertensive effect of lisinopril compared with nifedipine in patients with mild to severe essential hypertension.

For several reasons, increasing numbers of patients with hypertension are treated with angiotensin-converting enzyme inhibitors and calcium channel blockers. In a twenty-four week, double-blind, randomized, parallel study, the antihypertensive effect of lisinopril (20 to 80 mg qd) and nifedipine (20 to 80 mg bid) were compared in 21 patients. Fourteen patients received lisinopril (mean dose 35 mg), and 7 patients received nifedipine (mean dose 54 mg). By the end of week 12, 8 patients had responded (supine diastolic pressure less than or equal to 90 mg) to lisinopril and 5 to nifedipine. At the end of the study supine systolic/diastolic blood pressure was reduced from 172/104 to 149/92 mmHg with lisinopril and from 171/102 to 158/94 mmHg with nifedipine. No significant difference between the two treatments was detected. Three patients were reported to have at least one clinical adverse experience during the active treatment period, 1 in the lisinopril group and 2 in the nifedipine group. No serious clinical adverse experiences were recorded. In conclusion, lisinopril and nifedipine are both effective in reducing blood pressure in patients with mild to severe hypertension. Lisinopril qd and nifedipine slow release bid produce similar decreases in blood pressure after twelve weeks of therapy and the safety profiles of the two drugs are similar.

Antihypertensive Agents↗
PubMed1992

Victimizers and their victims: children's conceptions of the mixed emotional consequences of moral transgressions.

4-8-year-old children's conceptions of the emotional consequences of moral transgressions were assessed in 2 experiments. In Experiment 1, most children expected victimizers to feel positive emotions and victims to feel negative emotions, but 8-year-olds who assessed victims first subsequently attributed less positive emotions to victimizers. Despite efforts to manipulate the salience of victims' losses in Experiment 2, children had similar expectations about the emotional consequences of transgressions. However, a developmental shift emerged: 4-year-olds attributed extremely positive emotions to victimizers due to the material gains produced by victimization, whereas 8-year-olds attributed less positive emotions to victimizers, in part due to the unfairness and harm produced by victimization. Probe questions revealed that older children also attributed additional negative-valence emotions to victimizers, suggesting that victimizers are expected to feel conflicting rather than exclusively positive emotions. Discussion focused on potential cognitive constraints in children's conceptions of moral emotions.

Awareness↗
PubMed1991

Metabolic denitrosation of N-nitrosamines: mechanism and biological consequences.

NADPH-dependent microsomal metabolism of N-nitrosamines results in both oxidative dealkylation and denitrosation of the molecule. For denitrosation, two enzymatic mechanisms have been proposed: (i) cytochrome P450 (P450)-dependent one-electron reduction of the nitrosamine molecule, resulting in the formation of nitric oxide (NO) and secondary and primary amine, and (ii) liberation of NO via an oxidative mechanism mediated by a P450-dependent one-electron abstraction. In order to clarify the mechanism of denitrosation, the metabolism and kinetics of N-nitrosodibenzylamine (NDBzA) and its corresponding secondary amine dibenzylamine were studied. The main metabolites of NDBzA are benzaldehyde, the primary amine benzylamine and nitrite. An important finding is that benzaldehyde is generated more rapidly from dibenzylamine than from the parent NDBzA. During reductive denitrosation of NDBzA, the oxygen atom in benzaldehyde is derived from air, while benzaldehyde generated via the oxidative mechanism of denitrosation receives its oxygen atom from water due to hydrolysis of the intermediary benzylidenebenzylamine. Microsomal incubation of NDBzA in buffer containing 18O-H2O resulted in no incorporation of 18O from water into benzaldehyde, which could be related to the formation of the corresponding benzaldehyde, which could be related to the formation of the corresponding benzylidenebenzylamine. It is concluded that NDBzA is denitrosated by the proposed reductive mechanism. Current belief is that denitrosation leads to detoxification of the NA molecule; however, toxic effects cannot be excluded if the conversion of NO into NO2- and NO3- involves intermediary formation of the NO2 radical.(ABSTRACT TRUNCATED AT 250 WORDS)

Biotransformation↗
PubMed1990

Activation of epileptic foci by transcranial magnetic stimulation: effects on secretion of prolactin and luteinizing hormone.

Transient elevation of serum levels of prolactin has been observed following several types of epileptic seizures and after electrical stimulation of limbic temporal lobe structures via implanted electrodes. Transcranial magnetic stimulation has been found to selectively induce epileptiform afterdischarges in the epileptic focus of candidates for epilepsy surgery who suffered from temporal lobe epilepsy. Lateralized serial transcranial magnetic stimulation was therefore used and serum levels of prolactin or luteinizing hormone were measured to find if it could be used as a non-invasive diagnostic tool. The investigation was performed on six patients and five healthy volunteers. In the patients the induction of epileptiform potentials was continuously monitored via subdural electrodes. A transient surge of prolactin and luteinizing hormone was found in only one patient, in whom a complex partial seizure was induced. Thus, transcranial magnetic stimulation appeared not to be helpful for the lateralization of the (primary) epileptic focus during presurgical evaluation.

Adult↗
PubMed1990

Purification and characterization of recombinant Rev protein of human immunodeficiency virus type 1.

Recombinant Rev protein of human immunodeficiency virus type 1 has been expressed in Escherichia coli and purified by ion-exchange and gel-filtration chromatography. Specific binding of the purified protein to the Rev-responsive element of the viral RNA is demonstrated. Physical characterization of the purified protein by circular dichroism and intrinsic fluorescence spectroscopy indicate that the protein preparation is suitable for structural analysis. Circular dichroism measurements show that the protein is approximately 40-45% alpha-helix. Tryptophan fluorescence measurements suggest that the single tryptophan residue is located near the surface of the protein. Gel-filtration chromatography of the protein indicates that it has an apparent molecular mass of 33,000 daltons. This suggests that the protein in solution forms a stable tetramer consisting of monomers having molecular mass of 13,000 daltons.

Chromatography, Gel↗
PubMed1989

Purification of biologically active human immunodeficiency virus rev protein from Escherichia coli.

A genetic approach was used to facilitate purification of human immunodeficiency virus (HIV) rev protein. A recombinant protein containing a stretch of six histidine residues at the amino terminus was engineered and overexpressed in Escherichia coli. Purification of greater than 95% was achieved in a single step using an immobilized metal ion chromatography with a resin that has selectivity for proteins with neighboring histidine residues. We show that the modified protein is both properly modified and biologically active.

Amino Acid Sequence↗
PubMed1989

The human immunodeficiency virus rev protein is a nuclear phosphoprotein.

The human Immunodeficiency virus rev protein is one of several key regulatory proteins involved in the control of viral structural protein synthesis and replication. In this report, we identify the 20-kDa rev protein as a nuclear phosphoprotein. Post-translational modification was observed solely on serine residues. In vitro kinase reactions utilizing a derivative of Rev purified from Escherichia coli identified a nuclear kinase capable of phosphorylating exogenously added rev protein. Our results suggest that the nuclear kinase activity observed in vitro is likely to be responsible for the in vivo post-translational modification of Rev.

Animals↗
PubMed1989

Who benefits most from respite care?

This study examines the effect of five measures of utilization of respite care services (desire to use respite care services, actual use, accessibility, scheduling and helpfulness) upon mothers' coping resources. Using the analysis of variance between utilization measures and coping resources with the following intervening variables as covariates--mothers' self-esteem, family cohesion and adaptation, and clients' and mothers' characteristics--it was found that respite care acts as a differential service that can enhance coping resources (i.e., stress reduction skills) and is of most benefit to high self-esteem mothers of young developmentally disabled children. A home-based model was found to be the most beneficial to mothers in terms of enhanced coping resources. Findings are interpreted with respect to their implications for research, program model, planning and intervention.

Adaptation, Psychological↗