To investigate in vivo expression of chemokines in normal and inflamed human corneas, to determine whether chemokines are responsible for the recruitment of inflammatory cells. Methods:In situ hybridization of the CXC chemokines growth-related oncogene-␣ (Gro-␣) (CXCL-1), interleukin 8 (CXCL-8), macrophage interferon-␥ inducible gene (CXCL-9), and interferon-␥ inducible protein 10 (CXCL-10) and of the CC chemokines macrophage chemoattractant protein 1 (MCP-1) (CCL-2), macrophage inflammatory protein 1␣ (CCL-3), and regulated on activation, normal T-cell expressed and secreted (CCL-5) was performed to localize chemokine messenger RNA. Immunohistochemistry was used to identify the cellular infiltrate within the cornea. Three normal human eyes were compared with eyes enucleated because of chronic inflammation (n = 10), secondary to perforating injuries.Results: In normal corneas, no chemokine expression was detected. In inflamed lesions, a high intensity of sig-nals from Gro-␣ (CXCL-1) and MCP-1 (CCL-2) messenger RNA was observed in limbal epithelium and from Gro-␣ (CXCL-1), interleukin 8 (CXCL-8), and MCP-1 (CCL-2) in corneal stroma. The Gro-␣ (CXCL-1) was the only chemokine expressed by central corneal epithelium. All other examined chemokines were only moderately expressed in limbus and corneal stroma, or barely detectable.Conclusions: These cytokines are important agents in the cytokine network and contribute to the cell-specific and spatially restricted recruitment of neutrophils and mononuclear cells in acute inflammatory lesions of the human cornea.Clinical Relevance: Understanding the role of chemokines in corneal inflammation may lead to the development of a selective receptor blockage of highly expressed chemokines to inhibit the recruitment of leukocyte subsets.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder occurring at a rate of between 1/5,000 and 1/10,000 births in most European countries. The phenotype results from the degeneration of the anterior horn cells of the spinal cord, resulting in symmetrical muscle weakness and wasting. The disorder can be classified according to the severity of the disease and the age of onset into three major types. Two candidate SMA genes, NAIP and SMN, isolated from the 5q13 region, have been reported to be homozygously deleted in approximately 30% and >95% of SMA patients, respectively. Black SMA patients have been reported to have facial muscle weakness more commonly. This study aimed to determine the molecular basis of SMA in South African black SMA patients. The SMN gene was found to be homozygously deleted in 65.5% (19/29) of patients, significantly less frequently than in previous studies. Similarly, the NAIP gene was homozygously deleted in a smaller number, 14% (4/29) of patients; 47% (9/19) of SMN deletion patients appeared to have deletions of telomeric exon 7, but not exon 8. In at least six of these patients a gene conversion event has occurred. No detectable deletions were found in 35% (10/29) of patients. Haplotype analysis in the nondeletion patients, using six closely linked markers, provided no evidence for a founder mutation. No mutations were found in exons 3 and intron 6 through exon 8 by sequence analysis of these nondeletion patients. It is proposed that the differences in the SMA phenotype observed in black patients may in part be explained by a different molecular basis.

We report the response of ten patients (6 male, 4 female) with steroid-resistant focal segmental glomerulosclerosis (FSGS) to treatment with intravenous pulse cyclophosphamide (IVCP) together with oral prednisone. All patients had been treated with 60 mg/m2 oral prednisone daily for 2 months upon initial presentation. IVCP was given monthly at a dose of 500 mg/m2 over 6 months. Oral prednisone was given concurrently at 60 mg/m2 daily for 2 months and then on alternate days for 4 months, followed by 30 mg/m2 on alternate days for 6 months. Prednisone was then tapered monthly by 10 mg and finally discontinued. Five patients failed to respond to steroids from the onset and were considered as primary steroid resistant. Two of these patients achieved sustained remission after IVCP, one patient showed a partial response, with loss of edema, normalization of serum albumin, and persistent proteinuria, while two patients showed no response to IVCP. The other five patients had achieved remission after 2 months of daily prednisone at 60 mg/m2 upon initial presentation, but had suffered from more than three relapses per year and had eventually become steroid resistant. They were considered secondary steroid resistant. All five patients achieved sustained remission after IVCP. None of our patients suffered from adverse effects of IVCP. We suggest IVCP as an adjunctive therapy for steroid-resistant FSGS, particularly for patients with secondary steroid resistance.