Detection of Characteristic Phosphatidylcholine Containing Very Long Chain Fatty Acids in Cerebrospinal Fluid from Patients with X-Linked Adrenoleukodystrophy.

X-linked Adrenoleukodystrophy (X-ALD) is a rare genetic neurological disorder caused by a mutation of the ABCD1 gene that encodes a peroxisomal ABC protein ABCD1. ABCD1 has a role in transporting very long chain fatty acid (VLCFA)-CoA into the peroxisome for ß-oxidation. ABCD1 dysfunction leads to reduced VLCFA ß-oxidation and in turn increased VLCFA levels in the plasma and the cells of all tissues; these increased plasma levels have been used to diagnose X-ALD. It has been reported that plasma VLCFA is not correlated with the severity and disease phenotype of X-ALD. Therefore, we cannot predict the disease progression by the plasma VLCFA level. Cerebrospinal fluid (CSF) is constantly produced by brain, and thus levels of lipids containing VLCFA in CSF might be informative in terms of assessing X-ALD pathology. LC-MS/MS-based analysis showed that phosphatidylcholine (PC) containing VLCFA signals, such as PC 40 : 0(24 : 0/16 : 0), PC 42 : 0(26 : 0/16 : 0), PC 44 : 4(24 : 0/20 : 4) and PC 46 : 4(26 : 0/20 : 4) were characteristically detected only in the CSF from patients with X- ALD. In the present study, we analyzed limited number of patient's CSF samples (2 patients with X-ALD) due to the limitations of the availability for CSF samples from this rare disease. However, our finding would offer helpful information for studying the disease progression biomarkers in X-ALD. To our knowledge, this is the first report of analyzing lipids containing VLCFA in CSF from patients with X-ALD.

[PSA bounce phenomenon after transperineal interstitial permanent prostate brachytherapy for localized prostate cancer].

PURPOSE: We described the temporarily increase phenomenon in prostate-specific antigen level (PSA bounce) after transperineal interstitial permanent prostate brachytherapy (TIPPB) for localized prostate cancer. MATERIALS AND METHODS: From December 1998 to May 2003, 500 consecutive patients with localized prostate cancer were treated with TIPPB using iodine-125 or palladium-103. We examined 200 patients who have more than 2-year PSA follow-up. Median follow-up length was 1,069 days (range, 712-1,411 days). No patient received neoadjuvant or adjuvant hormone therapy. PSA determinations were performed every 3 months for the first 2 years after procedure, and every 6 months hereafter. PSA bounce was defined as an increase of 0.1 ng/ml or greater above the preceding PSA level after implant followed by a subsequent decrease below that level. The American Society for Therapeutic Radiology and Oncology (ASTRO) consensus panel criteria 1996 were used to define biochemical failure. RESULTS: PSA bounce was observed in 40% (80/200) of the cases receiving TIPPB. The median time to PSA bounce was 13 months from the day of implant. The median magnitude of the PSA bounce was 0.3 ng/ml from the pre-bounce level. Twelve cases demonstrated biochemical failure according to the ASTRO consensus guidelines of three consecutive rises in PSA. Ten of these subsequently showed a drop in PSA, consistent with biologic control of their disease. Two cases remain classified as apparent biochemical failures. CONCLUSIONS: A transient rise in the PSA following TIPPB, the so-called "bounce" is a common occurrence. The apparent PSA control of ten of twelve cases failing by the ASTRO criteria raises some concern. Further observation will be necessary to determine ways to discriminate these from true disease progression.

Molecular analysis of Physarum haemagglutinin I: lack of a signal sequence, sulphur amino acids and post-translational modifications.

The cDNAs encoding haemagglutinin I from plasmodia of Physarum polycephalum have been cloned using PCR protocols. The composite haemagglutinin I cDNA sequence, derived from several overlapping clones from PCR fragments, spans 408 nt and the 315 bp ORF encodes a polypeptide of 104 aa without a typical signal sequence. The putative molecular mass deduced from the amino acid sequence (10,760.76 Da) corresponds exactly to that determined by electrospray ionization MS (10,759.86 +/- 0.15 Da), suggesting that haemagglutinin I is not subject to post-translational modification. Haemagglutinin I lacks sulphur amino acids and has a beta-sheet as the major secondary structure. Expression of the coding sequence in Escherichia coli yielded a product that exhibits the same sugar-binding specificity as natural haemagglutinin I. The deduced amino acid sequence shows little similarity to that of any known lectins and thus apparently represents a novel type of lectin.