Nadine Urquhart

Nonketotic hyperglycinemia. Glycine accumulation due to absence of glycerine cleavage in brain.

Glycine concentrations were measured in plasma and cerebrospinal fluid of five patients in different types of hyperglycinemia to determine why severe neurologic deterioration is confined to the so-called nonketotic form of hyperglycinemia. Glycine content and glycine-cleavage enzyme activity were also determined in brain obtained in autopsy from three of these patients. Spinal-fluid glycine concentrations were 15 to 30 times above normal in patients with nonketotic hyperglycinemia, but were normal in those with hyperglycinemias of undetermined type who had comparable elevations of plasma glycine. Glycine content was two to four times above normal in several brain regions, and brain glycine cleavage enzyme activity was absent in two patients dying of nonketotic hyperglycinemia. By contrast, glycine content was normal and glycine cleavage activity present in the brain of an infant who died of hyperglycinemia of unknown cause. These results suggest that elevated glycine levels may be harmless in blood, but lethal in brain.

GABA content and glutamic acid decarboxylase activity in brain of Huntington's chorea patients and control subjects.

—GABA contents are significantly decreased in the caudate nucleus, putamen‐globus pallidus, substantia nigra, and occipital cortex in autopsied brain from Huntingtons chorea patients, as compared to values in the same regions from control subjects who have died without neurological disease. Homocarnosine levels are lower in choreic than in control brain, but only in the putamen‐globus pallidus and the cerebellar cortex are the differences significant.

Passage of taurine into adult mammalian brain

WE HAVE recently studied an unusual inherited human neurological disorder in which the content of taurine in autopsy specimens of brain was significantly decreased (paper in preparation). In an effort to devise a rational form of therapy for this disease, it became important to learn whether taurine administered to a patient could be expected to enter brain cells. The highly polar character of taurine does not suggest that this amino acid would readily cross the blood-brain barrier. However, PECK & AWAPARA (1967) , reported finding both C3’S] and [14C] labelled taurine in rat brain after the corresponding radioactive taurines had been injected intraperitoneally. The experiments described below confirm these investigators’ findings, and suggest that it may be possible to correct a taurine deficiency in human brain by repeated oral administration of taurine.

An Unusual Case of Severe Hypertriglyceridemia and Splenomegaly

A 49-year-old man of Japanese and British ancestry was referred to a metabolic diseases clinic for evaluation 5 months after nontraumatic spleen rupture requiring splenectomy. Prior history included hypertension and mild frontal headaches, but no other neurological or cardiovascular symptoms. The patient did not smoke and used alcohol infrequently. His mother had coronary artery disease, and his father had mild hypertension. There was no family history of consanguinity, splenomegaly, diabetes, or developmental delay. The ruptured spleen weighed 727 g, and splenomegaly was associated with marked sinus histiocytosis spreading apart the lymphoid component. The overwhelming majority of histiocytes were foamy (Fig. 1a⇓ ), and only a few had sea-blue appearance and reacted positively with periodic acid-Schiff (PAS), PAS and diastase, and May-Giemsa stains. A lipid storage disorder was suspected, but the histiocytes did not have the cytoplasmic linearity appearance of Gaucher cells and were otherwise nonspecific. Before splenic rupture, the patient’s lipoprotein profile was reported as being normal, with no past recorded triglyceride measurement exceeding 2 mmol/L. Figure 1. Pathology and genomic studies of the index patient. (a), Hematoxylin and eosin–stained section (40×) of spleen, showing expanded white pulp displacing Malpighian bodies. The pallor is due to the abundance of foamy histiocytes in the sinusoids, seen in inset (400X). (b), LightCycler (Roche Diagnostics) analysis of genomic DNA with curve C representing the patient’s APOE melting curve at codon 158, showing heterozygosity at codon 158 for 1 TGC trinucleotide (cysteine) with Tm of 56.4 °C and 1 indeterminate trinucleotide coding sequence with a melting temperature of 62.99 °C, which was outside the Cys158 acceptable range of 63.5–68.5 °C, indicating another amino acid encoded by this residue. Melting curves for normal E2/E4 (A) and E2/E3 (B) controls are shown for reference. (c), Direct sequencing of the patient’s plasmid cloned APOE alleles showing inframe deletion …

Corroboration of the Prozone Phenomenon in IgG4‐Related Disease: Comment on the Article by Khosroshahi et al

ing in RA. Hence, it would be of considerable interest to ascertain the clinical benefit of selective TNFRI blockade, especially when compared with TNF ligand blockade, which inhibits both TNFRI and TNFRII. Moreover, other investigators have highlighted the differential TNFRI/II requirements in autoimmune and inflammatory physiologic processes and speculate that TNFRI-specific blockade might be more effective, because it would leave the potentially beneficial TNFRII signaling pathway intact (2–4). Supported by GlaxoSmithKline.