Insights from latent partition analysis into categories inherent in wellness-illness

How health–disease is perceived or conceptualized is important for nursing research There is increasing evidence that individual representations are important in constructing the experience of health–disease What is the personal saliency of health–disease for the individual? To explore the patterns of meaning inherent in health–disease, a card sort was undertaken among 15 healthy individuals and 15 individuals with chronic renal disease Both groups were given 28 cards to sort twice once for when they felt ‘well’ and again for when they felt ‘ill’ The theoretical basis underlying the items of the card sort was a model of wellness-illness being developed Latent partition analysis was used to cluster the concepts from each data set followed by multi-dimensional scaling to analyse the structure of the intercategory probability estimates A possible unidimensional pattern of meaning (harmony) emerged for the ‘well’ data and a two-dimensional pattern (disharmony and optimism) for the ‘ill’ data This represents a preliminary step in the development of a theoretical model that would permit assessment of the meaning of health–disease for the individual     

Chemotherapy of L1210 and L1210/ARA-C leukemia with 5-aza-2′-deoxycytidine and 3-deazauridine

Summary The in vitro and in vivo antineoplastic activity of 5-aza-2-deoxycytidine (5-AZA-dCyd) and 3-deazauridine (3-DU) against L1210 and L1210/ARA-C (resistant to cytosine arabinoside) leukemic cells were investigated. L1210/ARA-C cells were more sensitive to the inhibitory effects of 3-DU than L1210 cells. Deoxycytidine completely reversed the in vitro cytotoxic effects produced by 3-DU on L1210 cells, but not those produced in L1210/ARA-C cells. L1210/ARA-C cells, which are deficient in deoxycytidine kinase, were completely resistant to the antileukemic effects of 5-AZA-dCyd, whereas this analogue produced a very potent antileukemic effect against L1210 cells. To study the in vivo interaction of 5-AZA-dCyd and 3-DU with respect to drug resistance, mice were simultaneously injected i. v. with 10⁴ L1210 cells plus 10² L1210/ARA-C cells. A 9-h i. v. infusion of 5-AZA-dCyd (12.8 mg/kg) or 3-DU (186 mg/kg) produced an increase in life span of 56% and 26%, respectively. However, the sequential administration of 5-AZA-dCyd followed by 3-DU produced a 265% increase in life span and 7/10 longterm survivor, a very potent antileukemic effect. These results suggest that 3-DU is an excellent agent for use in combination chemotherapy to overcome drug resistance to the deoxycytidine analogue, 5-AZA-dCyd.This investigation was supported by grant MA-6356 from the Medical Research Council of Canada and by LEUCAN     

Hyper-recombination and mutator effects of the mms9-1, mms13-1, and mms21-1 mutations in Saccharomyces cerevisiae

Summary Spontaneous mitotic intragenic and intergenic recombination at various sites is enhanced 10 to 100 fold in the methyl methanesulfonate (MMS)-sensitive mutants mms9-1, mms13-1, and mms21-1 of Saccharomyces cerevisiae. All three mutants show elevated rates of spontaneous mutation. Sporulation is reduced in diploids homozygous for any of the three mutations, and a deficiency in meiotic recombination and meiotic chromosome segregation is observed. Pleiotropic effects on cell viability, growth rate, and radiation sensitivity, in combination with the alterations in recombination and mutagenesis displayed by mutant strains, suggest that the MMS9, MMS13, and MMS21 genes play important roles in DNA replication and/or genetic recombination.     

Contribution of peripheral N-methyl-D-aspartate receptors to c-fos expression in the trigeminal spinal nucleus following acute masseteric inflammation

In this study, we examined the contribution of N-methyl-D-aspartate (NMDA) receptors on c-fos expression in the trigeminal brainstem nuclei following acute muscle inflammation. Mustard oil (MO; 20%, 30 microL) injected into the masseter muscle induced extensive peripheral edema and Fos-like immunoreactivity (Fos-LI) in several trigeminal brainstem areas including the subnucleus caudalis of the trigeminal spinal nucleus (Vc), the ventral and dorsal regions of the Vc/subnucleus interpolaris transition zone, and the paratrigeminal nucleus. In order to assess the effect of antagonizing NMDA receptors on MO-induced Fos-LI, rats were pre-treated with two different doses of i.v. MK-801 (0.3 mg/kg, 3 mg/kg), a non-competitive NMDA receptor antagonist, 30 min prior to MO injection. Additional groups of rats received MK-801 (0.3 mg/kg) directly in the masseter muscle or in the biceps muscle 5 min prior to MO injection. A higher dose of i.v. MK-801 (3 mg/kg) and MK-801 given locally into the masseter muscle (0.3 mg/kg) produced a significant reduction in total number of MO-induced Fos-LI. Further analyses revealed that pre-treatment with MK-801 (3 mg/kg i.v.) significantly reduced the Fos-LI all throughout the Vc. Only at the caudal Vc, there was a dose-dependent reduction of MO induced Fos-LI. Pre-treatment with masseteric MK-801 also significantly reduced the Fos-LI in the caudal Vc, with the effect greater than that produced by the same dose of MK-801 given intravenously. These results suggest that peripheral NMDA receptors contribute to nociceptive processing from craniofacial muscles.     

Different strains of Mycobacterium tuberculosis cause various spectrums of disease in the rabbit model of tuberculosis

The rabbit model of tuberculosis has been used historically to differentiate between Mycobacterium tuberculosis and Mycobacterium bovis based on their relative virulence in this animal host. M. tuberculosis infection in market rabbits is cleared over time, whereas infection with M. bovis results in chronic, progressive, cavitary disease leading to death. Because of the innate resistance of commercial rabbits to M. tuberculosis, 320 to 1,890 log-phase, actively growing inhaled bacilli were required to form one grossly visible pulmonary tubercle at 5 weeks. The range of inhaled doses required to make one tubercle allows us to determine the relative pathogenicities of different strains. Fewer inhaled organisms of the M. tuberculosis Erdman strain were required than of M. tuberculosis H37Rv to produce a visible lesion at 5 weeks. Furthermore, with the Erdman strain, only 7 of 15 rabbits had healed lesions at 16 to 18 weeks; among the other animals, two had chronic, progressive cavitary disease, a phenotype usually seen only with M. bovis infection. Genotypic investigation of the Erdman strain with an H37Rv-based microarray identified gene differences in the RD6 region. Southern blot and PCR structural genetic analysis showed significant differences between M. tuberculosis strains in this region. Correlation of the relative pathogenicity, including disease severity, in the rabbit model with the strain genotype may help identify stage-specific M. tuberculosis genes important in human disease.     

Thymus Ontogeny in Frogs: T-Cell Renewal at Metamorphosis

Metamorphosis in amphibians presents a unique problem for the developing immune system. Because tadpoles are free-living, they need an immune system to protect against potential pathogens. However, at metamorphosis, they acquire a variety of new adultspecific molecules to which the tadpole immune system must become tolerant. We hypothesized that Xenopus laevis tadpoles may avoid potentially destructive antiself responses by largely discarding the larval immune system at metamorphosis and acquiring a new one. By implanting triploid (3N) thymuses into diploid (2N) hosts, we examined the influx and expansion of host T-cell precursors in the donor thymus of normally metamorphosing and metamorphosis-inhibited frogs. We observed that donor thymocytes are replaced by host-derived cells during metamorphosis, but inhibition of metamorphosis does not prevent this exchange of cells. The implanted thymuses export T cells to the spleen. This donor-derived pool of cells declines after metamorphosis in normally developing frogs but is retained to a greater extent if metamorphosis is inhibited. These studies confirm previous observations of a metamorphosis-associated wave of expansion of T cells and demonstrate that it is not dependent on the relatively high concentrations of thyroid hormones required for metamorphosis. Although some larval T cells persist through metamorphosis, others may be destroyed or the larval population is significantly diluted by the expanding adult population.     

Monoclonal anti-(T,G)-A—L antibodies: Characterization of fine specificity and idiotype expression

The technique of polyethylene glycol mediated cell fusion was used to establish 22 monoclonal cell lines secreting anti-(T,G)-A—L antibody. Cell lines were derived from C3H.SW and B10 mice and produced antibody with light chains and predominantly γ₁, heavy chains. Fine-specificity analysis demonstrated that 15 cell lines made antibodies that also recognize a determinant present on GAT, GT (9:1) and GT (1:1), whereas little, if any, serum antibody demonstrates this cross-reaction. Fourteen antibodies, derived from both B10 and C3H.SW mice, bear idiotypic determinants defined by Lewis anti-[B10 anti-(T,G)-A—L], but only two, both from C3H.SW mice, react with Lewis anti-[C3H.SW anti-(T,G)-A—L]. Adsorption studies indicate that no hybridoma tested bore the complete set of idiotypic determinants defined by either serum.     

Presence of Rickettsia conorii subsp. israelensis, the causative agent of Israeli spotted fever, in Sicily, Italy, ascertained in a retrospective study

A retrospective analysis by molecular-sequence-based techniques was performed to correctly identify the etiological agent of 24 Mediterranean spotted fever cases occurring in Western Sicily, Italy, from 1987 to 2001. Restriction analysis of a 632-bp PCR-amplified portion of the ompA gene allowed presumptive identification of five clinical isolates as belonging to Rickettsia conorii subsp. israelensis, the etiological agent of Israeli spotted fever (ISF). The remaining 19 rickettsial isolates were Rickettsia conorii subsp. conorii, the only pathogenic rickettsia of the spotted fever group reported in Italy until the present. Sequence analysis of the ompA gene confirmed the identification of all the R. conorii subsp. israelensis isolates and demonstrated that rickettsiosis caused by R. conorii subsp. israelensis can be traced back to 1991 in Sicily. The recorded clinical data of the five ISF patients support the idea that these strains could correlate to more-severe forms of human disease. Three of five patients experienced severe disease, and one of them died.     

Human herpesvirus 8 infection among various population groups in southern Israel

OBJECTIVE: To compare the prevalence of antibodies to human herpesvirus 8 (HHV-8) or Kaposi sarcoma-associated herpesvirus among Israeli and Ethiopian subjects. METHODS: Serum samples were obtained from 98 Israeli Jewish students aged 18-30 years, 100 HIV-1-seronegative Ethiopian immigrants to Israel of the same age, and 100 HIV-1-seronegative Ethiopian children 1-12 years old upon their arrival in southern Israel. Plasma samples were obtained from 3 hospitalized patients with multicentric Castleman disease (MCD) as positive controls. All serum samples were tested for antibodies to both latent and lytic antigens. Antibodies to the lytic antigens and the latency-associated nuclear antigen (LANA) of HHV-8 were detected by enzyme linked immunosorbent assay and by immunofluorescence assay. HHV-8 DNA from serum or plasma samples was detected by polymerase chain reaction analysis. RESULTS: Antibodies to HHV-8 LANA were detected in 2.9% of the Israeli subjects aged 18-30 years and in 26% of the Ethiopian subjects from both age groups tested. Antibodies to the lytic antigens were detected in all 3 MCD patients, in 4% of the Ethiopian children, and in 2% of the 18- to 30-year-old Ethiopians. No antibodies to the lytic antigens were detected in the Israeli students. HHV-8 DNA was detected in all 3 MCD patients and in 2 of 4 of the Ethiopian children positive for the lytic antigens. CONCLUSIONS: HHV-8 is highly prevalent in Ethiopian immigrants to Israel as compared with Israeli students. Antibodies to HHV-8 in Ethiopia are acquired before puberty. The results of this study indicate the association of HHV-8 with MCD, as has been documented by many other researchers.