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Canada's government gained constitutional autonomy from Britain in the 1960s and decriminalized abortion for a few women under the strict control of doctors and hospitals. When the Supreme Court ruled this law unconstitutional in 1988, it marked a complete success for the women's movement activists. They were able to seal this victory by stopping, barely, the attempts by the Conservative government to return abortion law to the criminal code. The movement developed its political clout without the help of numerous women's policy agencies that, although sympathetic to feminist goals and well‐funded, were silenced by the policy environment.

Long-term renal transplant function is limited primarily by a progressive scarring process loosely termed "chronic rejection, chronic allograft nephropathy, or allograft fibrosis." Although the etiology of transplant fibrosis is uncertain, several possible factors including chronic cyclosporin A (CsA) exposure may contribute to its pathogenesis. CsA stimulates renal fibrosis perhaps through the induction of the potent pro-sclerotic growth factor, transforming growth factor beta (TGFbeta). Previously, we demonstrated that, in human transplant biopsies, acute CsA toxicity but not acute tubular necrosis is associated with elevated levels of renal TGFbeta protein. We now examine whether long-term CsA treatment (1 year) is associated with elevated levels of intra-allograft TGFbeta and whether heightened expression of TGFbeta is clinically significant.Using immunohistochemical techniques, we determined the relative level of expression of intrarenal TGFbeta protein in transplant biopsies. We studied biopsies obtained from 40 CsA-treated patients that were diagnosed as having chronic allograft fibrosis. Biopsies were scored as having minimal or high levels of TGFbeta.Seventy-two percent of patients expressed high levels of intra-allograft TGFbeta. This group of patients lost renal function at an average rate of -19.5+/-17.3 ml/min/year. In contrast, patients with minimal or no TGFbeta expression experienced a decline of only -6.2+/-4.1 ml/min/year (P=0.01).These results suggest that the majority of CsA-treated patients with biopsy proven chronic fibrosis have elevated levels of intra-graft TGFbeta that correlates with an increased rate of decline in renal function.

The long-term side effects of lifelong steroid immunosuppression are well documented, therefore, steroid withdrawal (SW) if safe would clearly be of benefit. From 1987-1996, 470 kidney transplants were performed at our institution. During this time period, steroid withdrawal was offered to a select group of patients (n = 43) who were at least 1 year post transplant (27.6 +/- 12.0 months, 15-64 months), had stable graft function and had experienced only mild episodes of rejection in the postoperative period. Informed consent was obtained from all participants. Twenty-five patients were male and 18 were female. The mean age at time of transplantation was 42.4 +/- 14.1 years (17-65 years). There were 28 cadaveric renal transplants (CRT), 10 living related kidney transplants (LRT) and 5 simultaneous kidney-pancreas transplants (SPK). Maintenance immunosuppression in all patients consisted of CSA 3-5 mg/kg, and AZA 1-2 mg/kg. Twenty-nine patients (67%) have remained off steroids with good renal function for 13-59 months (38.3 +/- 11.0). Steroids were restarted in 14/43 (32%) patients 1-36 months post SW (13.3 +/- 11.0 months). Eight of these 14 patients had a rise in creatinine and biopsy proven rejection, 5 of whom responded to reinstitution of steroid immunosuppression, and have stable renal function (CR = 2.0 +/- 0.4) 41-53 months (45 +/- 4.0 months) post SW. Three (7%) patients lost their allograft. One was a SPK recipient who retained good pancreatic function and subsequently received a successful 2nd kidney transplant. The other 2 patients died awaiting retransplantation. Steroids were recommenced in 6/14 patients who did not develop rejection for inability to tolerate CSA/AZA (2), anxiety (2) or recurrent disease (2). In the majority of our patients, (93%) SW did not result in immunologic graft loss. A graft loss of 7% (3) is not significantly different from the expected graft loss in a kidney transplant recipient population over a time period of 9 years. Therefore, we feel that with careful monitoring steroid withdrawal can be safely accomplished in select patients.

The gene (mT5AP) encoding murine type-5 acid phosphatase has been isolated and completely sequenced while the gene (hT5AP) encoding human T5AP has been partly sequenced. The murine gene spans 4 kb and contains five exons. Exon 1 is completely non-coding and exon 2 starts with the initiation codon in both mT5AP and hT5AP. The positions of the intron/exon boundaries are completely conserved between mT5AP and hT5AP, but are distinct from the gene encoding the related porcine protein, uteroferrin (Utf). There is strong homology at both the nucleotide (nt) and amino acid (aa) levels between the inferred mouse cDNA and the sequences of rat T5AP and hT5AP, and pig Utf. The mT5AP and hT5AP genes were found to have multiple transcription start points (tsp) by primer extension analysis, consistent with the absence of a consensus TATA box. The sequences for the 5'-flanking regions of mT5AP and hT5AP were determined to -1.6 and -1.0 kb, respectively, relative to the tsp. A 2-kb segment of the mT5AP 5' flanking region linked to a luciferase-encoding reporter gene (Luc) was sufficient to direct tissue-specific transcription in the mouse macrophage cell line, RAW264. Significant sequence similarity between the mT5AP and hT5AP promoters is restricted to the most proximal 200 bp, which also resembles the porcine Utf gene, and a 300-bp segment 700 bp upstream. A progesterone-response element is present only in the mouse promoter and the estrogen- and iron-response elements described previously in the pig gene are absent from both the mouse and human genes. These differences may result in distinctive regulation of T5AP and Utf expression.

To compare clinical and histopathological data and outcome of patients with dermatomyositis (DM) with and without interstitial lung disease (ILD).Patients diagnosed with definite DM were prospectively evaluated. Clinical and analytical data were recorded and muscle biopsies were performed. In patients with respiratory symptoms an extensive pulmonary evaluation was done.104 patients were diagnosed with idiopathic inflammatory myopathy, 63 with DM. Eight of the patients with DM (13%) also had associated ILD. Arthralgia and fever were more frequently seen in the ILD group and there was no associated malignant condition. Either atypical or nonspecific cutaneous lesions were more frequently seen in ILD patients. Anti Jo-1 antibodies were positive in 75% of the patients with ILD and in 3% of patients with DM without ILD (p0.001). Bronchoalveolar lavage measured for cell count showed an increased lymphocyte count in 3/5 cases in which this data was recorded. Lung biopsies showed interstitial pneumonitis in 2 cases and desquamative interstitial pneumonitis in one. All patients achieved complete remission of muscular involvement. With respect to lung disease, 4/8 obtained complete remission, and the other 4 showed partial improvement. No significant statistical differences in terms of survival were found between the 2 groups.ILD associated with DM represents a subgroup of DM with clinical and biological differences. However, such patients do not have poorer prognosis than patients without ILD if they are managed aggressively with immunosuppressive drugs.