Nutritional status in patients with phenylketonuria using glycomacropeptide as their major protein source.

BACKGROUND/OBJECTIVES: Low phenylalanine (PHE), glycomacropeptide-based protein substitute (GMP) is an alternative to traditional L-amino acid supplements (AA) used in the dietary management of phenylketonuria (PKU). In a retrospective, longitudinal study, we report the nutritional status of PKU patients taking AA and GMP. SUBJECTS/METHODS: Eleven PKU patients aged 27±10 years (1 HPA, 4 mild and 6 classical PKU) on dietary treatment were evaluated (anthropometry, body composition, blood pressure measurements, biochemical markers including vitamin, mineral, lipids, carbohydrates and protein status/metabolism, and nutritional intake assessment) at two different annual reviews. The mean time taking AA was 13±5 months and GMP 13±7 months. Blood phenylalanine (PHE) and tyrosine (TYR) were analysed before and after GMP introduction. RESULTS: Both GMP and AA protein substitutes provided similar protein equivalent intake (0.85 vs 0.75 g/kg/day, P=0.182). In the GMP group, it contributed 57% (27-100%) of the protein substitute intake (with AA delivering the rest of protein substitute intake), providing an additional 34±12 mg/day PHE. Nutritional intake, anthropometry and body composition measurements were similar in both the groups. Median blood PHE did not change (P=0.594), although values within target range improved (36 vs 46%), but this was not statistically significant. Mean blood TYR increased (52.0±19.2 vs 63.2±25.6 µmol/l, P=0.033), and all biochemical markers remained stable, except for a lower A1C haemoglobin (P=0.011). CONCLUSIONS: Partial GMP contribution to total protein substitute intake did not affect nutritional status in patients with PKU. Blood PHE control was not adversely affected. The increased blood TYR after GMP introduction necessitates further study.

The ultimate nanoscale mincer: assembly, structure and active sites of the 20S proteasome core.

20S proteasomes constitute the proteolytic core of large protease complexes found in all branches of life. Among these, the eukaryotic 26S proteasome ubiquitously poses as a vital final entity in regulated degradation of intracellular proteins. The composition of 20S core particles has been disclosed in detail, facilitated by groundbreaking studies on ancestral prokaryotic 20S proteasomes of low complexity and culminated in the crystal structure determination of the much more complex eukaryotic particles. This article first summarizes insights into the structural organization of the 20S core followed by characterization of its proteolytic activities, which are confined to the central cavity of the particle. In eukaryotes they reside in three different subunit types differing in their preference for cleavage sites in substrates as well as in their importance for the proteasome's cellular function. The second part reviews current knowledge on the biogenesis pathways of 20S core particles, which have to ensure not only the fixed subunit arrangement but also activation of proteolytic subunits in a late assembly state.

Malignant granular cell tumor of the vulva in a 17-year-old: Case report and literature review.

Granular cell tumors are uncommon soft tissue tumors. Although the majority of these tumors are benign, a rare malignant variant exists which is aggressive, with local recurrence rates up to 70% and 3-year survival rates of less than 50%. We present a case of malignant granular cell tumor of the vulva in a 17-year-old, the sixth such case to be reported at this site. She was treated with a left hemivulvectomy and ipsilateral groin node dissection followed by postoperative radiation therapy. She remains free of disease at 16 months. Patients with malignant granular cell tumor or granular cell tumor of malignant potential are best managed with wide local excision and regional lymph node dissection.

Ump1p is required for proper maturation of the 20S proteasome and becomes its substrate upon completion of the assembly.

We report the discovery of a short-lived chaperone that is required for the correct maturation of the eukaryotic 20S proteasome and is destroyed at a specific stage of the assembly process. The S. cerevisiae Ump1p protein is a component of proteasome precursor complexes containing unprocessed beta subunits but is not detected in the mature 20S proteasome. Upon the association of two precursor complexes, Ump1p is encased and is rapidly degraded after the proteolytic sites in the interior of the nascent proteasome are activated. Cells lacking Ump1p exhibit a lack of coordination between the processing of beta subunits and proteasome assembly, resulting in functionally impaired proteasomes. We also show that the propeptide of the Pre2p/Doa3p beta subunit is required for Ump1p's function in proteasome maturation.

Accumulation of a lectin-like breakdown product of beta-conglutin catabolism in cotyledons of germinating Lupinus albus L. seeds.

During germination of Lupinus albus seeds, a 20-kDa polypeptide accumulates in the cotyledons of 4-d-old plants (Ferreira et al., 1995b, J Exp Bot 46: 211-219). Immunological, polypeptide cleavage with cyanogen bromide and amino acid sequencing experiments indicate that the 20-k-Da polypeptide and ubiquitin are structurally unrelated. However, there is a strong sequence homology between the 20-kDa polypeptide and the vicilin-like storage proteins from pea and soybean. Our results indicate that the 20-kDa polypeptide is an intermediate breakdown products of beta-conglutin catabolism, the vicilin-like storage protein from L. albus, and that its interaction with anti-ubiquitin antibodies results from the recognition of the antibodies by the 20-kDa polypeptide rather than by the opposite. Besides rabbit anti-ubiquitin antibodies, the 20-kDa polypeptide interacts with a variety of glycoproteins, including immunoglobulin G from several animal species, peroxidase and alkaline phosphatase, suggesting that it possess a lectin-type activity. Its activity is resistant to sodium dodecyl sulfate or methanol treatments, boiling and autoclaving. Purification of the 20-kDa polypeptide and immunological studies with anti-20-kDa-polypeptide antibodies showed that the non-glycosylated polypeptide is part of a glycoprotein with an estimated molecular mass of 210 kDa, composed of several types of structurally related subunit with molecular masses ranging from 14 to 50 kDa. Purified native protein containing the 20-kDa polypeptide self-aggregates in a calcium-dependent manner as reported for some glycosylated lectins. The possible physiological function of the 20-kDa polypeptide is discussed.

Pulse cyclophosphamide in the treatment of neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: The effect of pulse cyclophosphamide treatment was retrospectively assessed in 25 systemic lupus erythematosus (SLE) patients with central nervous system involvement. All patients who tested positive for anti-phospholipid antibodies and/or lupus anticoagulant were excluded. RESULTS: Low-dose intravenous cyclophosphamide pulses (500 mg) were administered weekly in all patients. Twenty-four out of 25 patients attained a good response (after a mean of 11 days). Cyclophosphamide was well tolerated in all patients with only minor side effects. None of the patients experienced ovarian failure, cystitis or herpes zoster. CONCLUSIONS: Weekly low-dose cyclophosphamide pulses appear to be safe and effective for the management of neuropsychiatric manifestations in SLE patients without antiphospholipid antibodies.