In Canada, health and safety laws are built around three worker rights which are not guaranteed by law in the United States: the right to participate in joint management-worker health and safety committees; the right to know about workplace hazards which requires consultation with the joint committee about the education and training programs; and the right to refuse hazardous work. In the context of NAFTA, health, safety and environmental laws and their enforcement, as well as the workers' compensation system, are all under attack by business leaders who cite the need to deregulate and privatize Canadian institutions in order to harmonize with the United States. The counteroffensive by the trade unions and their allies in the social justice movement is described; the struggle continues.

Canada↗

PubMed1996

Presence of an insulin-like growth factor I autocrine loop predicts uterine fibroid responsiveness to tamoxifen.

Uterine leiomyoma is an estrogen-responsive tumor, and the present studies examine the ability of the antiestrogen tamoxifen to modulate leiomyoma cell growth. Tamoxifen is an effective form of hormonal therapy for breast cancer, although the mechanism by which tamoxifen inhibits tumor growth is not well understood and may involve mechanisms other than the action of tamoxifen as an estrogen antagonist. Tamoxifen was found to inhibit the proliferation of three of five leiomyoma-derived cell lines (ELT cell lines) in vitro, including an estrogen receptor-negative cell line. The ability of tamoxifen to decrease leiomyoma growth was found to correlate with expression of insulin-like growth factor I (IGF-I) by the tumor cells, suggesting that the inhibitory effects of tamoxifen were associated with expression of this growth factor. The existence of an IGF-I autocrine loop in the cells was investigated, because transcripts for both IGF-I and its cognate receptor were expressed in the tamoxifen-responsive cell lines. An IGF-I RIA demonstrated secreted IGF-I protein in serum-free medium conditioned by the IGF-I-expressing cell line ELT 3, and this same medium supported the growth of IGF-requiring MCF-10A cells, indicating the presence of biologically active IGF-I in the conditioned medium. Exogenous IGF-I stimulated ELT 3 cell proliferation, confirming that this growth factor is mitogenic for leiomyoma cells. IGF-I neutralizing antibody inhibited ELT 3 growth, indicating that the levels of IGF-I produced by the leiomyoma cells were physiologically significant. These data demonstrate the existence of an IGF-I autocrine loop in tamoxifen-sensitive leiomyoma cells, supporting the hypothesis that the presence of an IGF-I autocrine loop predicts uterine fibroid responsiveness to tamoxifen.

Animals↗

PubMed1996

Renal cell carcinoma development in the rat independent of alterations at the VHL gene locus.

Germline alterations of the human von Hippel-Lindau (VHL) tumor suppressor gene predispose to renal cell carcinoma and a constellation of other tumor types found in VHL disease. This gene is also mutated or deleted in a high proportion of sporadic nonpapillary renal cell carcinomas. In the Eker rat model, spontaneous renal cell carcinoma develops with a high frequency. We therefore investigated the role of this tumor suppressor gene in the development of these hereditary rat tumors. By using reverse transcriptase (RT)-polymerase chain reaction (PCR) analysis, the sequence of the rat VHL gene was determined over the portion of the gene homologous to regions where most mutations in the human VHL gene occur. The sequence homology was 90% and the amino-acid identity 99% between the rat and human genes. A developmental and tumor-specific pattern of expression for the VHL gene was found; a ubiquitous 3.2-kb transcript was expressed in all rat tissues examined (neonatal kidney, lung, liver, brain, heart, kidney, spleen, testis, and stomach), and an additional 4.5-kb transcript was expressed in neonatal kidney and cell lines derived from Eker rat renal cell carcinomas (ERC cell lines). To determine whether mutations in the VHL gene were involved in tumor development in the Eker model, RT-PCR, single-strand conformation polymorphism (SSCP) analysis, and direct sequencing were used to search for alterations in this gene in the ERC cell lines. Alterations in the VHL gene were not detected by SSCP, and these data were confirmed by direct sequencing. Transformed rat kidney epithelial cell lines derived from Fisher rats also expressed the VHL gene but like the ERC cell lines did not contain mutations in the VHL gene. These data indicate that in the rat, transformation of kidney epithelial cells and the development of solid, nonpapillary renal cell carcinoma can occur via pathways that are independent of alterations at the VHL gene locus.

Animals↗

PubMed1996

Inhibition of estrogen-stimulated growth of uterine leiomyomas by selective estrogen receptor modulators.

Uterine leiomyoma is the most frequent gynecologic neoplasm in women. By using a panel of cell lines derived from spontaneous Eker rat leiomyomas, we examined the estrogen-responsive phenotype of these tumor cells. Leiomyoma-derived ELT cell lines proliferated in response to estrogen, and estrogen-induced cell proliferation could be inhibited by the estrogen antagonist ICI 182780 and the selective estrogen-receptor modulators (SERMs) raloxifene and tamoxifen. In addition to inhibiting cell growth, these antagonists also inhibited estrogen-induced increases in progesterone-receptor expression. These data indicate that SERMs such as raloxifene and tamoxifen act as estrogen antagonists in uterine myometrial cells and suggest that this class of compounds may be effective for treatment of this important gynecologic neoplasm.

Animals↗

PubMed1996

Electromagnetic field induced changes in lipid second messengers.

Initial studies with a human hematopoietic cell line, TF-1, suggest multifarious effects of electromagnetic fields on lipid signal transduction. We have examined the effects of pulsed magnetic fields (2 T, 84 microseconds zero-to-peak haversine, 91 V/m induced electric field) on the cell cycle by flow cytometry. A 31% increase of cells in the G1 phase occurred concurrently with a 35% decrease of cells in S-phase, which suggests that doses of 30 or 40 pulses have an anti-proliferative effect. Changes in the lipid second messengers, diacylglycerol (DAG) and phosphatidic acid (PA) with stimuli of 2 T intensity were also dependent on the number of pulses. DAG production doubled with 30 pulses and tripled with 40 pulses, and PA levels were reduced to one third and one tenth of the original levels. Phospholipase D (PLD) up-regulation was assessed directly by the capacity of PLD to catalyze transphosphatidylation in the presence of alcohol. [3H]Phosphatidylethanol formed rapidly and continued to increase with concomitant decreases in [3H]PA and parallel generation of [3H]DAG. Propranolol, an inhibitor of PA phosphohydrolase, inhibited the formation of DAG in a dose-dependent manner with a marked increase in PA production. Examination of the kinetics of formation of [3H]choline and [3H]phosphocholine at different times after stimulation showed a rapid and consistent increase in [3H]choline, whereas [3H]phosphocholine increase was evident only 60 min after stimulation. Magnetic exposure also caused a shift in some molecular species patterns of DAG and PA which could be correlated with phosphatidylinositol, phosphatidylethanolamine and phosphatidylcholine molecular species decreases. Therefore, we propose that the PC-PLC pathway may be temporarily inactivated for a short period of time by exposure to pulsed stimuli, and the PC-PLD pathway is up-regulated based on: (1) cellular release of [3H]choline; (2) rapid intracellular formation of [3H]PA followed by [3H]DAG; (3)active transphosphatidylation; and (4) blockade of DAG formation by propranolol.

Cell Line↗

PubMed1996

An overview of the role of government in the organisation and provision of health services in Japan.

This article is illustrated with reference to health services in the Tokyo Prefecture. It seeks to describe the role of government in the organisation and provision of health services in Japan. It is based on experiences gained from a three-month placement at the Tokyo Metropolitan Government Bureau of Public Health in late 1994. Wherever possible the article identifies similarities and differences between the Japanese and Australian health care systems. Part of the analysis has been to identify areas where opportunities exist for Australian health service providers to develop further cooperation with particular sectors of the Japanese health system and also where the potential for the export of health services may exist. The health systems of Australia and Japan have points of similarity and difference. Essentially both systems operate within the context of a compulsory universal health insurance system. However, unlike Australia, the bulk of service provision in Japan is left to the private sector, while government retains the primary role of regulator. It is interesting to observe that while the Australian health care system is currently exploring options to expand the service range and level of participation of private sector services in health care delivery (within the context of universal health insurance), the Japanese health care system appears to be examining options through which further government intervention can improve service access and service efficiency. Japan presents opportunities to observe the benefits and disadvantages of predominantly private sector provision within the context of universal health insurance coverage.

Aged↗

PubMed1996

Radiation-induced genomic instability and persisting oxidative stress in primary bone marrow cultures.

There is accumulating evidence that cells exposed to low and often environmentally relevant doses of ionizing radiation survive the initial insult, but transmit genomic instability to their progeny. The underlying mechanism of radiation-induced genomic instability is unknown. We present bio-chemical evidence consistent with the hypothesis that enhanced and persistent oxy-radical activity may be responsible.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1996

Identification of selected gamma-ray induced deficiencies in zebrafish using multiplex polymerase chain reaction.

The ease with which mutations can be generated in zebrafish makes this vertebrate an important resource for developmental genetics and genome studies. We have developed a PCR-based screening method that allows the efficient identification of gamma-ray induced deficiencies targeted to selected sequences. We describe three mutants characteristic of our findings and show that these mutations include deletions and translocations that can affect as much as 1% of the genome. These deficiencies provide a basis for analyzing the functions of cloned zebrafish genes using noncomplementation screens for point mutations induced by high-efficiency chemical mutagenesis.

Animals↗

PubMed1996

True identity of control Staphylococcus aureus strains and their performance in the tube coagulase test.

One hundred laboratories were asked to submit their control Staphylococcus aureus strains to determine the true identity of strains presumed to be S. aureus NCTC 6571, and also to evaluate the performance of those strains being used as controls in the tube coagulase test (TCT). Of the 60 who replied, 55 laboratories sent at least one strain labelled as S. aureus NCTC 6571 (total of 64 strains). Of these, 84% were identified as S. aureus, and were indistinguishable from a fresh type strain by a combination of phenotypic methods including biotyping, antibiotic susceptibility testing and phage typing. Six-to-ten strains (9-16%), depending on the degree of stringency, were not identifiable as S. aureus NCTC 6571. The time since last retrieval from storage ranged from daily to > or = 3 years, but there was no correlation between this duration and the likelihood of differing from S. aureus NCTC 6571. Forty-seven laboratories submitted 51 strains used as controls in the TCT; these included 31 strains labelled as S. aureus NCTC 6571, eight wild strains, three other NCTC strains and nine strains of uncertain origin. Generally, the S. aureus NCTC 6571 strains produced weaker clots than the remainder. None of the S. aureus NCTC 6571 strains was found to be inoculum dependent but four of the other control strains were. The study demonstrates that some laboratories must improve procedures for ensuring that control S. aureus strains retain their true identity, particularly by avoiding repeated subcultures. Laboratories are divided in their use of strong or weak (S. aureus NCTC 6571) positive controls for the TCT. S. aureus NCTC 6571 is a more stringent control for the TCT than other control strains presently being used and is, therefore, to be preferred.

Anti-Bacterial Agents↗

PubMed1996

Oral diseases, mycology and periodontal microbiology of HIV-1-infected women.

HIV-1 infection is increasing more rapidly among heterosexual women. Relatively limited information is available on HIV-related oral pathoses in these individuals. To gain insight into the type and occurrence of oral lesions in this population, 25 HIV-1 infected women including asymptomatic, symptomatic and AIDS patients were examined clinically and sampled for detection of oral yeast and characterization of their subgingival microbial flora. Sixty percent of the subjects were African-American, with 80% infected via heterosexual contact. Oral candidiasis was the most common nonperiodontal oral lesion, observed in 44% of the patients. Oral yeast was cultured from all women with candidiasis and 76% of the total subjects. Oral hairy leukoplakia was clinically diagnosed in 16% of the subjects. Clinically mild to moderate gingivitis and periodontitis were observed in 84% and 52% of the patients, respectively. Candidiasis and the presence of cultivable yeast were observed in patients with low, intermediate, and high CD4+ T lymphocyte numbers. Plaque samples were collected from each subject and enumerated by predominant cultivable methods, selective media and microscopy. No differences were detected in the microflora associated with seropositive women with existing periodontitis relative to those without periodontitis or to seronegative women with periodontitis. Candidiasis was the most notable oral clinical manifestation in the HIV-1-infected women and may be a useful clinical indicator of early immune dysfunction mediated by HIV-1.

AIDS-Related Opportunistic Infections↗

PubMed1996

A longitudinal study of lymphocyte subsets in a cohort of cats naturally-infected with feline immunodeficiency virus.

Despite the potential of feline immunodeficiency virus (FIV) as an animal model for human immunodeficiency virus (HIV) studies, the long term effects of naturally-occurring infection have not been determined. HIV infection causes an ongoing deterioration in immune function which directly correlates with disease, in particular acquired immunodeficiency syndrome (AIDS). However, it is not known whether FIV-induced immunosuppression is progressive or related to the clinical condition. This study examined changes in lymphocyte subset numbers of serial samples, taken from cohorts of FIV-positive and FIV-negative cats over and 18-month period. FIV-positive cats were clinically staged as asymptomatic carriers (AC) or cats with AIDS-related complex (ARC), and FIV-negative cats matched and staged on the basis of similar diseases. During the course of the study, 4 FIV-positive cats developed AIDS, classed as the terminal stage of infection. There were no significant differences in the mean absolute numbers of any lymphocyte subset between the onset (t0) and the completion (t18) of the study. Similarly there were no significant changes in subset numbers during the 18 months preceding the development of AIDS. While the study period was brief and the sample sizes small, it is postulated that FIV infection in Australia may not necessarily cause progressive immunodeficiency and that FIV-induced immunosuppression (as measured by subset analysis) may not be well correlated with the clinical status of the infected cat.

Animals↗

PubMed1996

A Combined Model for Growth and Subsequent Thermal Inactivation of Brochothrix thermosphacta.

A mathematical technique for integrating growth and thermal inactivation models of microorganisms into a smooth combined model that can be applied to circumstances under which the temperature gradually rises from growth to inactivation regions is described. For the death part of the model, a correction term is introduced to allow for additional resistance of the cells gained during slow heating. The model was validated with Brochothrix thermosphacta heated in broth at rising temperatures.

Journal Article↗

PubMed1996

Differential expression of alpha E beta 7 integrins on bronchoalveolar lavage T lymphocyte subsets: regulation by alpha 4 beta 1-integrin crosslinking and TGF-beta.

T lymphocytes expressing the alpha E beta 7 integrin are localized and selectively retained in mucosal tissues. To investigate a potential relationship between alpha E beta 7 expression and pulmonary inflammation, the distribution of alpha E beta 7-bearing CD4+ and CD8+ T cells in peripheral blood and bronchoalveolar lavage (BAL) fluids obtained from patients with allergic asthma, sarcoidosis, hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis (IPF) was determined. In contrast to the distribution in peripheral blood, BAL fluid from these patients contained high number of cells expressing alpha E beta 7 with markedly different expression patterns on CD4 or CD8 cells as well as among the various diseases. Despite similar numbers of activated CD4 cells, alpha E beta 7+CD4+ T cells ranged from 15% in asthmatics to 70% in IPF. In contrast, even in normal individuals, 60% to 90% of BAL fluid CD8+ T cells express alpha E beta 7, suggesting differential induction mechanisms on CD4 and CD8 cells. In vitro experiments revealed that a substantial proportion of peripheral blood CD+ T cells express alpha E beta 7 after stimulation with anti-CD3 antibodies, and up to 80% positive cells were found after the addition of TGF-beta. In contrast, less than 10% of CD4 cells express this particular integrin after in vitro stimulation, and the presence of TGF-beta only increased the number to 30%. Supernatants from in vitro-activated BAL cells as well as concentrated BAL fluid from patients with high alpha E beta 7 expression had no further enhancing effect. However, crosslinking of alpha 4 beta 1-, but not beta 2-integrins, significantly increased the number of alpha E beta 7 expressing CD4+ and CD8+ T cells, even in the absence of TGF-beta. These data indicate that in addition to TGF-beta, the interaction of particular T-cell subsets with specific endothelial cell and extracellular matrix proteins may upregulate alpha E beta 7 integrin expression and thereby contribute to the selective accumulation of these cells in inflammatory lung diseases.

Adult↗

PubMed1996

The chinless mutation and neural crest cell interactions in zebrafish jaw development.

During vertebrate development, neural crest cells are thought to pattern many aspects of head organization, including the segmented skeleton and musculature of the jaw and gills. Here we describe mutations at the gene chinless, chn, that disrupt the skeletal fates of neural crest cells in the head of the zebrafish and their interactions with muscle precursors. chn mutants lack neural-crest-derived cartilage and mesoderm-derived muscles in all seven pharyngeal arches. Fate mapping and gene expression studies demonstrate the presence of both undifferentiated cartilage and muscle precursors in mutants. However, chn blocks differentiation directly in neural crest, and not in mesoderm, as revealed by mosaic analyses. Neural crest cells taken from wild-type donor embryos can form cartilage when transplanted into chn mutant hosts and rescue some of the patterning defects of mutant pharyngeal arches. In these cases, cartilage only forms if neural crest is transplanted at least one hour before its migration, suggesting that interactions occur transiently in early jaw precursors. In contrast, transplanted cells in paraxial mesoderm behave according to the host genotype; mutant cells form jaw muscles in a wild-type environment. These results suggest that chn is required for the development of pharyngeal cartilages from cranial neural crest cells and subsequent crest signals that pattern mesodermally derived myocytes.

Animals↗