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Biomedical subjects

I Abraham

Publications and source records attributed to I Abraham.

At least 19 recordsLinked to original sources
PubMed1997

A descriptive study of elderly community-dwelling alcoholic patients in the rural south.

Alcohol-related disorders, estimated to be more prevalent in the South, are associated with serious comorbid disorders, such as depression and suicide. In a rural outreach program, the authors examined patients with a diagnosis of alcoholism and compared them with nonalcoholic patients on various demographic and descriptive variables. Of 166 patients referred to the program, 35 (21.1%) had an alcohol-related disorder. Alcoholism was significantly associated with male gender and younger age, but nearly half of the alcoholic subjects were women. Alcoholism is associated with inappropriate health care utilization; alcohol-related disorders produced significantly more emergency room visits and somewhat more hospital admission; these patients were less likely to have a primary care physician. No patient was receiving treatment for alcoholism.

Activities of Daily Living↗
PubMed1996

Seroepidemiological and leishmanin skin test surveys of visceral leishmaniasis in south and southwest Ethiopia.

Sero-epidemiological and leishmanin skin test surveys of visceral leishmaniasis were carried out in eight localities of South and Southwest Ethiopia between the July 1989 and June 1992. A total number of 4870 subjects comprising semi-pastoral nomads, peasants and farm labourers were included in the study. Areas of high and low leishmanin skin test positivity were identified, with rates varying from 1.0-80.5%. An enzyme-linked immunosorbent assay was used to determine prevalence of antileishmanial antibodies. The rates varied from 1.8% to 27.8%. Age and sex related serological and leishmanin skin test profiles are described. Correlation analysis of serological and leishmanin skin test was made for data in each locality. The relationships between seroprevalence, leishmanin skin test rates and prevalence of active visceral leishmaniasis and the implications on degrees of endemicity and patterns of transmission are discussed.

Adolescent↗
PubMed1995

Incidence, determinants, and consequences of subclinical noncompliance with immunosuppressive therapy in renal transplant recipients.

In this descriptive cross-sectional study, we investigated the incidence, determinants, and consequences of subclinical noncompliance with immunosuppressive therapy in 150 adult renal transplant recipients with more than one year posttransplant status. Symptom frequency and symptom distress, and self-care agency were measured by the Transplant Symptom Frequency and Symptom Distress Scale, and the Appraisal for Self-Care Agency Scale, respectively. The Long-Term Medication Behavior Self-Efficacy Scale and a renal transplant knowledge questionnaire were developed as part of this study to measure perceived self-efficacy and knowledge of the therapeutic regimen. Demographic variables were also measured. The incidence of subclinical noncompliance with immunosuppressive therapy as assessed by interview was 22.3%. Compliers and noncompliers differed significantly on the variables of marital status (P = 0.03), situational-operational knowledge (P = 0.02), self-care agency (P = 0.03), and perceived self-efficacy related to long-term medication intake (P = 0.048). A logistic regression model using gender, marital status, perceived self-efficacy, self-care agency, knowledge about medication administration and signs of infection, and situational operational knowledge as predictor variables, revealed a 78.6% correct classification of compliers versus noncompliers and a sensitivity ratio of 95.9%. There were significantly more acute late rejection episodes (P = 0.003) in the noncompliant group. Graft survival at 5 years in this group was also significantly lower (P = 0.03) than the compliant patients. No significant difference was found in terms of the occurrence of chronic rejection episodes or in terms of patient survival at 5 years. Because noncompliance is a risk factor for negative clinical outcome in renal transplant recipients, it is of utmost importance to develop intervention strategies to enhance compliance in this population by using determinants identified in exploratory studies.

Adult↗
PubMed1995

Leishmania aethiopica: experimental infections in non-human primates.

Six Cercopithecus aethiops monkeys, 4 Theropithecus gelada baboons and 2 Papio anubis baboons were infected using Leishmania aethiopica isolates originating either from localized (LCL) or diffuse (DCL) cutaneous leishmaniasis patients. The history of lesions in 4 C. aethiops monkeys infected by LCL strains mimicked the process in human LCL patients. Infection of 2 C. aethiops monkeys using a DCL strain resulted in localized, non-ulcerative, self-healing nodular lesions. Such lesions were also observed in 2 T. gelada baboons infected by LCL strains. Active lesions and healing in C. aethiops and T. gelada, after infection by LCL stains, were accompanied by positive DTH and immunity to challenge by LCL or DCL strains.

Animals↗
PubMed1994

K252a, KT5720, KT5926, and U98017 support paclitaxel (taxol)-dependent cells and synergize with paclitaxel.

We have used paclitaxel-dependent Tax 2-4 cells to screen for compounds that have paclitaxel-like functional activity. The indolocarbazole serine/threonine kinase inhibitor K252a and analogues such as KT5926, KT5720, and K252b partially support the growth of the paclitaxel-dependent cells in the absence of paclitaxel. A novel kinase inhibitor of similar structure, U98017, supports the growth of the dependent cells to 48% of that seen with paclitaxel. Used in combination with paclitaxel, these compounds reduce the amount of paclitaxel required for maximum growth of the dependent cells. Isobologram analysis demonstrates that these compounds also act synergistically with paclitaxel to promote toxicity in wild-type Chinese hamster ovary cells. These selected indolocarbazoles may act at sites distinct from that of paclitaxel and may specifically inhibit kinases that contribute to the destabilization of microtubules. Other indolocarbazoles such as staurosporine and rebeccamycin do not support paclitaxel-dependent cell growth. Structurally unrelated serine/threonine kinase inhibitors such as H-9 and H-7 or tyrosine kinase inhibitors such as lavendustin do not support the growth of these cells. These results define a screen for functional paclitaxel analogues and suggest that it may be useful to investigate the possible synergy of selected indolocarbazoles and paclitaxel in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Comparative bioavailability of clofazimine coevaporate in the pig.

The systemic availability of a solid dispersion (coevaporate) of clofazimine (CLF) in poly(vinyl methyl ether maleic anhydride) copolymer (PVM/MA) was tested in the pig. Single 100 mg oral doses of the coevaporate and the commercial product, Lamprene (Ciba-Geigy) were administered on separate occasions (separated by a two-week washout period) to four pigs (two males, two females) in a random cross-over study. Multiple plasma samples, obtained from an indwelling jugular-vein cannula, following drug administration, were analysed by an HPLC method for CLF. Pharmacokinetic analyses of the plasma CLF concentration-time data were performed. A paired t-test indicated significant differences (p < 0.05) between the coevaporate and Lamprene in the Cpmax, tmax, and AUC. The calculated relative systemic bioavailability (Frel) of CLF from the coevaporate, relative to that from Lamprene, was three. It is concluded that formulation of CLF, as a solid dispersion, may provide enhanced aqueous dissolution and systemic absorption and may also provide high therapeutic blood levels. These could lead to reduction in the current therapeutic doses and, consequently, minimization of drug-related side effects.

Animals↗
PubMed1994

V79 Chinese hamster lung cells resistant to the bis-alkylator bizelesin are multidrug-resistant.

Bizelesin (U-77779) is a highly potent bis-alkylating antitumor agent that is effective against several tumor systems in vitro and in vivo. V79 cells that were 125- to 250-fold resistant to bizelesin developed after constant exposure to gradually increasing concentrations of the drug. Resistant cells exhibited a multidrug-resistant phenotype and genotype as indicated by cross-resistant to several structurally and functionally unrelated drugs, e.g., colchicine, actinomycin D, and Adriamycin, and overexpression of mdr mRNA. Very low levels of cross-resistance to the alkylating agents cisplatin and melphalan were seen. Multidrug-resistant mouse leukemia (P388/Adriamycin-resistant) and human (KB/vinblastine-resistant) cells were also resistant to bizelesin. Bizelesin resistance was unstable and decreased when cells were grown in the absence of the drug. Resistant and sensitive cell lines had similar levels of glutathione, and bizelesin cytotoxicity for resistant cells was not markedly affected by treatment with buthionine sulfoximine. Cross-resistance between bizelesin and several of its analogs is reported.

Alkylating Agents↗
PubMed1994

Development of the long-term medication behaviour self-efficacy scale: qualitative study for item development.

There are no published instruments of patient self-efficacy related to medication behaviour, yet understanding and promoting medication compliance are central to nursing practice. The purpose of this quanlitative study was to explore patient perceptions, experiences and practices associated with long-term medication behaviour in order to establish an instrument measuring self-efficacy in medication behaviour. In-depth interviews were conducted with 14 patients with lifelong dependency on medicine. Using a phenomenological method of analysis the following themes emerged, all of which could be integrated within Bandura's conceptualization of dimensions of self-efficacy. The dimension of personal attributes comprised the themes of emotional distress, confidence in the physician, perceived health status, and normalcy. Environmental factors included the themes of routine, distraction, social support and cost of medication. The third dimension of self-efficacy, task-related and behavioural factors was composed of themes of side-effects, drug delivery system, medication aids, medication schedule, and knowledge. Based on these themes, items for the Long-Term Medication Behaviour Self-Efficacy Scale, were developed and integrated into a version that is currently being submitted to further psychometric work.

Adult↗
PubMed1993

Multidrug resistance is a component of V79 cell resistance to the alkylating agent adozelesin.

Adozelesin is a highly potent alkylating agent which has entered clinical trials based on its unique mechanisms of action and broad-spectrum antitumor activity in vivo. V79 cells resistant to adozelesin (V79/AdoR) were not resistant to the alkylating agent cisplatin but showed the phenotypic and genotypic characteristics of multidrug resistance. Thus V79/AdoR was cross-resistant to several structurally and functionally unrelated drugs, resistance was reversed by verapamil, and the resistant cell line expressed mdr mRNA and p170 glycoprotein. Also, adozelesin uptake and the amount of drug alkylated to DNA was much lower in the resistant cell line as compared to the sensitive parent. However, even with the same amount of drug bound to DNA (10 fmol/micrograms DNA) the survival of V79/S approximately 15% survival) was much lower than that of V79/AdoR (approximately 80%). Therefore the resistance of V79/AdoR cannot be explained solely by the multidrug resistance mechanism (i.e., lower drug uptake and less drug alkylation to DNA), which suggests that multiple mechanisms may account for resistance to adozelesin. V79/AdoR showed different levels of cross-resistance to several adozelesin analogues. The analogues could be divided into 2 groups; those with very low partition coefficients (log P < 2 as compared to 2.74 for adozelesin) had low levels of cross-resistance, whereas analogues with higher partition coefficients (log P > 2.4) were cross-resistant to adozelesin.

Alkylating Agents↗
PubMed1993

Staurosporine reduces P-glycoprotein expression and modulates multidrug resistance.

We have investigated the effect of staurosporine and other kinase inhibitors on the mRNA and protein levels of the P-glycoprotein (P-gp) in multidrug resistant (MDR) cells. Treatment of human MDR KB-V1 cells with staurosporine for 24 h caused up to a 50% decrease in the amount of P-gp mRNA and protein present. Co-treatment of KB-V1 cells with verapamil, a known reversal agent, plus staurosporine, H-9, or K252a resulted in an enhanced sensitization of cells to vinblastine than with verapamil alone. These findings support a role for protein kinases in the control of multidrug resistance through effects on P-gp levels.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Identification of a 170 kDa membrane kinase with increased activity in KB-V1 multidrug resistant cells.

Using an in situ kinase assay we have identified kinases that are elevated in some multidrug resistant cells. Kinases were detected by measurement of 32P incorporation in proteins that were renatured after being subjected to SDS-polyacrylamide gel electrophoresis and transferred to polyvinylidene difluoride membranes [Ferrell and Martin: J Biol Chem 264:20723-20729, 1989; Mol Cell Biol 10:3020-3026, 1990]. Kinases at 79, 84, and 92 kDa showed increased activity in the multidrug resistant human KB-V1 cells as compared to the sensitive parental KB-3-1 cells. The KB-V1 multidrug resistant cell line exhibited a 170 kDa membrane associated kinase activity that was not present in the parental drug sensitive line. The 170 kDa kinase activity was not affected by Ca++, phosphatidylserine, or cAMP, but was diminished after incubation in the presence of the kinase inhibitors staurosporine, K252a and KT5720. The 170 kDa kinase activity phosphorylated mainly threonine, with no evidence of tyrosine phosphorylation, and was not identical to either the multidrug resistance associated P-glycoprotein or the EGF receptor. Other multidrug resistant cell lines also showed elevated 170 kDa kinase activity, such as the human breast cancer MCF-7/Adr(R) and murine melanoma B16/Adr(R) cells, but the activity was not present in murine leukemia P-388 sensitive or multidrug resistant cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Non-glucocorticoid steroid analogues (21-aminosteroids) sensitize multidrug resistant cells to vinblastine.

Several members of a group of compounds developed to treat stroke and trauma of the central nervous system are shown also to reverse multidrug resistance in human KB-V1 cells. The most potent reversal agents studied are 21-aminosteroid derivatives (lazaroids), tirilazad mesylate (tirilazad, U-74006F) and U-74389F. Tirilazad sensitizes resistant human cells (KB-V1) to killing by vinblastine by 66-fold, but does not change the sensitivity of the nonresistant parental line, KB-3-1, to vinblastine. KB-V1 cell membranes have high levels of P-glycoprotein, a protein that acts as an efflux pump and is thought to be the major cause of multidrug resistance in these cells. Tirilazad inhibits the photoaffinity labeling of P-glycoprotein with [3H]azidopine in KB-V1 cells more effectively than does verapamil, a standard reversal agent. In addition, tirilazad causes the increased accumulation of [3H]vinblastine in multidrug resistant KB-V1 cells. Studies of the resistance reversal potential of related compounds suggest that the complex amine portion of tirilazad is important for its reversal activity, while the steroid portion is less important.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Reduced mRNA levels for the multidrug-resistance genes in cAMP-dependent protein kinase mutant cell lines.

We have previously shown that in Chinese hamster ovary (CHO) cells, a mutant cell line with a defective regulatory subunit (RI) for the cAMP-dependent protein kinase (Abraham et al: Mol. Cell. Biol., 7:3098-3106, 1987), and a transfectant cell line expressing the same mutant kinase, showed increased sensitivity to a number of drugs that are known to be substrates for the multidrug transporter (P-glycoprotein). In the current study we have investigated the mechanism by which cAMP-dependent protein kinase controls drug resistance. We report here that the sensitivity of the kinase defective CHO cell lines to multiple drugs results from decreased RNA levels for the multidrug-resistance gene. Similar results were obtained with mouse Y1 adrenal cells. Wild-type Y1 cells had high levels of P-glycoprotein due to expression of both the mdr1b and mdr2 genes, whereas the cAMP-dependent protein kinase mutant Kin 8 cells had decreased RNA levels for these genes. A Kin 8 transfectant with restored cAMP-dependent protein kinase activity recovered mdr expression, indicating a cause and effect relationship between the protein kinase mutations and mdr expression. No changes in nuclear run-off assays could be detected, suggesting a non-transcriptional mechanism of regulation. Wild-type Y1 cells are more drug sensitive despite having higher levels of P-glycoprotein than the mutant cells. This paradoxical result may be explained by the higher rate of synthesis of steroids by the wild-type Y1 cells, which appear to be inhibitors of P-glycoprotein transport activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗