Tissue-specific regulation of pyroglutamate aminopeptidase II activity by thyroid hormones

Among the enzymes capable of degrading thyrotropin-releasing hormone (TRH) in vitro, two pyroglutamate aminopeptidases (PGA) are specific for TRH: thyroliberinase, a seric enzyme and PGAII, a membrane-bound peptidase. The effect of thyroid hormone status on the activity of these enzymes was evaluated in serum and various tissues. Only in adenohypophysis, triiodothyronine treatment increased PGAII to 376% of control; hypothyroidism produced the reverse effect (decrease to 23% of control). As previously reported, similar changes were observed for thyroliberinase. TRH degradation at the adenohypophysis level may participate in the negative feedback control of thyroid hormones.     

Variables that affect the expansion rate and outcome of small abdominal aortic aneurysms

Seventy-three patients with small (less than 6 cm in diameter) abdominal aortic aneurysms (AAAs) were selected for nonoperative management and followed up with sequential ultrasound size measurements. Fifty-four men and 19 women, 51 to 89 years of age (mean 70 years), had an initial mean AAA size of 4.1 cm (anteroposterior) x 4.3 cm (lateral) diameter, with a calculated elliptic cross-sectional area of 14.3 cm2. After a mean of 37 months of follow-up, AAA area increased at a mean rate of 20% per year (3 cm2 yr; 0.4 to 0.5 cm/yr diameter). Expansion rate was not affected by initial aneurysm size. During follow-up, only 3 patients (4%) required urgent operation (1 died), 26 patients (36%) died of non-AAA causes, and 26 patients (36%) underwent elective AAA repair because of progressive size increase (1 died). Elective operations were performed at the rate of 10% per year, when mean AAA size had increased to 22 cm2 (5.1 cm in diameter). Multiple regression analysis of clinical parameters available at presentation indicated that subsequent elective AAA repair was predicted by younger age at diagnosis and larger initial aneurysm size. As anticipated, patients who underwent surgery had more rapid aneurysm expansion (5.3 cm2/yr) compared with patients who did not undergo surgery (1.6 cm2/yr; p less than 0.05). This difference was caused by more rapid expansion during later follow-up intervals among patients selected for operation and was not predicted by the change in aneurysm size observed during initial ultrasonographic follow-up. Final aneurysm size was predicted by initial size, duration of follow-up, and both systolic and diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mosaic ring 12p and total anomalous pulmonary venous return

An infant born with total anomalous pulmonary venous return (TAPVR) was found to have an extra chromosome present as a small ring. Spectral karyotyping and FISH analysis identified the material as a duplication involving the short arm of chromosome 12. Previous cases describing a variety of cytogenetic abnormalities that have been associated with TAPVR are reviewed along with prior cases of duplication 12p with their associated findings. We believe ours is the first case to report the occurrence of mosaic ring 12p and its association with TAPVR.     

An efficient SNP system for mouse genome scanning and elucidating strain relationships

A set of 1638 informative SNP markers easily assayed by the Amplifluor genotyping system were tested in 102 mouse strains, including the majority of the common and wild-derived inbred strains available from The Jackson Laboratory. Selected from publicly available databases, the markers are on average ~1.5 Mb apart and, whenever possible, represent the rare allele in at least two strains. Amplifluor assays were developed for each marker and performed on two independent DNA samples from each strain. The mean number of polymorphisms between strains was 608±136 SD. Several tests indicate that the markers provide an effective system for performing genome scans and quantitative trait loci analyses in all but the most closely related strains. Additionally, the markers revealed several subtle differences between closely related mouse strains, including the groups of several 129, BALB, C3H, C57, and DBA strains, and a group of wild-derived inbred strains representing several Mus musculus subspecies. Applying a neighbor-joining method to the data, we constructed a mouse strain family tree, which in most cases confirmed existing genealogies.     

Extrasynaptic receptors on cell bodies of neurons in central nervous system of the leech.

1. A systematic study has been made of the sensitivity of identified sensory and motoneurons in the leech central nervous system to chemical transmitter substances. 2. The following substances elicited responses from the cell bodies of individual neurons: acetylcholine, 5-hydroxytryptamine, gamma-aminobutyric acid, glutamic acid, glycine, dopamine, and norepinephrine. Since the cell bodies of leech neurons are free of synapses, the receptors that give rise to these responses are extrasynaptic. 3. Sensory and motoneurons of different function had characteristic complements of extrasynaptic receptors. For example, mechanosensory cells responding to light touch, to pressure, and to noxious stimuli could be distinguished by their responses to iontophoretically applied compounds. For one of these modalities (nociceptive), neurons with different receptive fields but otherwise similar properties had markedly distinct extrasynaptic receptors. The possible significance of extrasynaptic receptors is discussed.     

Alteration in expression of beta 2 integrins on lamina propria lymphocytes in ulcerative colitis and Crohn's disease

We have previously demonstrated by immunohistochemistry that mucosal expression of beta 2 integrins was enhanced in Crohn's disease and ulcerative colitis as compared to normal controls. We aimed, therefore, to determine whether there was a corresponding alteration in the expression of CD11a/CD18 (LFA-1), the primary lymphocyte beta 2 integrin, among the principal subsets of lamina propria lymphocytes (LPLs). Accordingly, LPLs were extracted from surgical resection specimens derived from patients with Crohn's colitis, ulcerative colitis, and from noninflamed controls. Following immunofluorescent staining, three-color flow-cytometry analysis identified LPLs on the basis of CD45 side scatter gating, which in turn, were further subdivided into CD4(+), CD8(+), and CD19(+) cells to account for the predominant T and B cells in the lamina propria. Expression patterns of CD11a, the alpha-subunit of LFA-1; CD18, the beta-subunit of LFA-1; and alpha d, a novel alpha-subunit of the beta 2 integrin family were assessed for each of these lymphocyte subsets. In Crohn's disease and ulcerative colitis there was an increased mean percentage expression of CD4(+) cells and CD11a(+) cells compared with noninflamed controls. CD11a was more likely to be expressed on CD4(+) cells in both Crohn's disease and ulcerative colitis and compared with controls and less expressed on CD19(+) cells. It is likely that an influx of CD4(+)11a(+) cells into the lamina propria accounted for these changes. These results suggest that although currently there is great interest in harnessing alpha 4 beta 7 in treatment of inflammatory bowel disease, further consideration should be given to the role of CD11a in these disease states.