Induction of apoptosis by remoxipride metabolites in HL60 and CD34+/CD19- human bone marrow progenitor cells: potential relevance to remoxipride-induced aplastic anemia.

The antipsychotic agent, remoxipride [(S)-(-)-3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2,6-dimethoxybenz amide] has been associated with acquired aplastic anemia. We have examined the ability of remoxipride, three pyrrolidine ring metabolites and five aromatic ring metabolites of the parent compound to induce apoptosis in HL60 cells and human bone marrow progenitor (HBMP) cells. Cells were treated for 0-24 h with each compound (0-200 microM).

Genotype-phenotype relationships in studies of a polymorphism in NAD(P)H:quinone oxidoreductase 1.

The NAD(P)H:quinone oxidoreductase 1 (NQO1) genotype-phenotype relationship was examined in individuals with a polymorphism in NQO1. The polymorphism comprises a C to T base change at position 609 of the human NQO1 cDNA (C609T) and codes for a proline to serine substitution in the amino acid structure of the NQO1 protein. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis of genomic DNA.

The diagnosis of multiple sclerosis: Peplau's Interpersonal Relations Model in practice.

Multiple sclerosis (MS) is a chronic, frequently progressive neurological disease of unknown etiology and uncertain trajectory. Physicians and nurses have historically been uncomfortable broaching the topic of a possible MS diagnosis with patients and have tended instead to talk about it in euphemistic terms. However, with the development of therapeutic agents that may be more effective early in the disease course, the early communication of diagnostic and treatment information has become increasingly important.

Urinary tract infections may trigger relapse in multiple sclerosis.

Multiple Sclerosis (MS), a demyelinating disease of the central nervous system, is the most common neurological disease affecting young adults in North America and, in the majority of cases, is associated with accumulating disability. Urinary tract dysfunction affects up to 90% of the MS population, and urinary tract infections are encountered in up to 74% of the tested population. Viral infections have previously been shown to trigger acute exacerbation and it is our experience that urinary tract infection also commonly precedes relapse, and, when recurrent, is associated with neurologic progression.

Responding to reported clusters of common diseases: the case of multiple sclerosis.

Reports of disease clustering are becoming ever more common, and there is increasing pressure on public health agencies to respond rapidly and appropriately to these reports. We investigated a cluster of five cases of MS occurring in a small multidisciplinary hospital department. Data were collected by a variety of methods, including measurement and description of the workplace, completion of survey instruments by department staff, and construction of case histories of persons with MS.

Learned helplessness in the multiple sclerosis population.

The purpose of this cross-sectional, descriptive study was to describe the relationships between learned helplessness and disease status, functional and social disability, and disease activity in the multiple sclerosis population. Additionally, the relationships between learned helplessness and age, disease duration, education and marital and employment status were evaluated. Self-report instruments with established validity and reliability in the multiple sclerosis population were used to collect the data.

Vasopressin resistance in chronic renal failure. Evidence for the role of decreased V2 receptor mRNA.

Studies were performed to determine the mechanism underlying deficient arginine vasopressin (AVP)-stimulated adenylyl cyclase activity in chronic renal failure (CRF). As compared to control, principal cells cultured from the inner medullary collecting tubule of rats previously made uremic by 5/6 nephrectomy fail to accumulate cAMP when stimulated with AVP. CRF cells do respond normally to forskolin or cholera toxin and the defect in AVP responsiveness is not prevented by treatment with pertussis toxin, by cyclooxygenase inhibition, or by inhibition or down-regulation of protein kinase C.

Mutant quantity and quality in mammalian cells (AL) exposed to cesium-137 gamma radiation: effect of caffeine.

We examined the effect of caffeine (1,3,7-trimethylxanthine) on the quantity and quality of mutations in cultured mammalian AL human-hamster hybrid cells exposed to 137Cs gamma radiation. At a dose (1.5 mg/ml for 16 h) that reduced the plating efficiency (PE) by 20%, caffeine was not itself a significant mutagen, but it increased by approximately twofold the slope of the dose-response curve for induction of S1- mutants by 137Cs gamma radiation.

Interaction of metals during their uptake and accumulation in rabbit renal cortical slices.

The uptake and accumulation of metals occurs in the kidney, which is a key site for interaction between metal nephrotoxicants. The uptake/accumulation and interaction of CdCl2, HgCl2, K2Cr2O7, and NaAsO2 was examined in precision-cut rabbit renal cortical slices. Slices were incubated with 10(-6) to 10(-3) M of a single metal toxicant or combinations of metal toxicants for 12 hr in DME-F12 media.

Mechanism of cisplatin nephrotoxicity in rat renal proximal tubule suspensions.

The effect of the nephrotoxic antineoplastic agent, cisplatin, on isolated rat renal proximal tubule suspensions was examined. [(195m)Pt]Cisplatin (31.7 mum) uptake was progressive over a 5-hr incubation period to a maximum value of 8.

Examination of the structure-toxicity relationships of L-cysteine-S-conjugates of halogenated alkenes and their corresponding mercapturic acids in rat renal tissue slices.

Rat kidney slices were produced using a modified version of a mechanical tissue slicer. The slices were incubated with various concentrations of L-cysteine conjugates and mercapturic acids of halogenated alkenes in a submersion incubation system. The slices showed a time- and concentration-dependent toxicity to the nephrotoxic conjugates.