Urinary excretion of 5-L-oxoproline (pyroglutamic acid) is increased in normal adults consuming vegetarian or low protein diets

A method for measuring 5-L-oxoproline in urine, which involves isolation by short-column chromatography, acid hydrolysis to glutamic acid and enzymic assay of glutamic acid, was used to measure the rate of excretion in normal adults, aged 20 to 45 y. There was no difference in the daily excretion between omnivorous males (217 micromol/d) and females (195 micromol/d). In vegetarian males, urinary 5-L-oxoproline (404 micromol/d) was significantly greater than in vegetarian females (267 micromol/d, P = 0.013). Compared with omnivorous males or females, excretion of 5-L-oxoproline was significantly greater in vegetarian males (P < 0.0001) and females (P= 0.005). When normal adults consumed a diet in which the protein content was controlled at either 4.0 or 6.2 g N/d for 5 d, there was a significant increase in urinary 5-L-oxoproline on d 5, compared with either d 1 or 4. There was a significant inverse linear relationship between the increased urinary 5-L-oxoproline on the fifth dietary day and the nitrogen content of the diet. On the basis of this relationship, when the urinary excretion of 5-L-oxoproline (320 micromol/d) for vegetarians was predicted from an estimate of their dietary intake of nitrogen, the estimate was, on average, close to the measured value (345 micromol/d). As a matter of course, vegetarians excrete more 5-L-oxoproline in urine than do omnivores, and we speculated that this difference might be accounted for by differences in dietary nitrogen and the endogenous capacity for de novo synthesis of glycine.     

Inhibition of gastric emptying and intestinal transit by amphetamine through a mechanism involving an increased secretion of CCK in male rats

1. The effect of amphetamine on gastrointestinal (GI) transit and the plasma levels of cholecystokinin (CCK) were studied in male rats. 2. Gastric emptying was inhibited both acutely and chronically by the administration of amphetamine. GI transit was decreased by the acute administration of amphetamine but not affected by the chronic administration of amphetamine. 3. Plasma CCK levels were increased dose-dependently by amphetamine. 4. Proglumide, a CCK receptor antagonist, prevented amphetamine-induced inhibition of gastric emptying and the decrease in GI transit in male rats. 5. The selective CCK(A) receptor antagonist, lorglumide, dose-dependently attenuated the amphetamine-induced inhibition of gastric emptying in male rats. In contrast, the selective CCK(B) receptor antagonist, PD 135,158, did not reverse the effect of amphetamine on gastric emptying. 6. Both lorglumide and PD 135,158 reversed the inhibitory effect of amphetamine on GI transit in male rats. 7. These results suggest that amphetamine-induced inhibition of gastric emptying and intestinal transit is due in part to a mechanism associated with the hypersecretion of endogenous CCK.     

Double level fractures of the femur treated with closed intramedullary nailing

Breast cancer patients receiving tamoxifen (Tam) are at an increased risk for developing endometrial carcinomas, possibly due to the partial estrogenic effect of Tam on endometrial cells. Progestational therapy has not routinely been included in Tam regimens. It was our aim to determine the presence of estrogen receptors (ERs) and progesterone receptors (PRs) in normal and abnormal endometria from postmenopausal women with breast cancer who were treated with Tam. Standard immunohistochemical staining of ERs and PRs was performed on paraffin sections from formalin-fixed uterine curettings or hysterectomy specimens from 40 patients who had received 20-40 mg of Tam daily for a minimum of 3 months. For comparison, normal endometria from 20 women who had not received Tam (11 premenopausal, 9 postmenopausal) were also studied for ER and PR expression. Staining was evaluated using semiquantitative immunoreactivity scores (IRS) ranging from 0 (negative) to 12 (strongly positive). In the group of patients receiving Tam, ERs and PRs were detected in the nuclei of glandular cells in 24/24 cases of endometrial atrophy (ER/PR-IRS, 2-12), in 8/8 endometrial polyps (ER-IRS, 6-12; PR-IRS, 4-12), in 4/4 adenomatous endometrial hyperplasias (ER-IRS, 3-8; PR-IRS, 1-12), and in 4/4 well-differentiated endometrioid adenocarcinomas (ER-IRS, 2-12; PR-IRS, 6-8). Of the 11 endometria from premenopausal patients who had not received Tam, 8 were ER+/PR+ (ER-IRS, 1-12; PR-IRS, 1-12), 1 was ER+/PR- (ER-IRS, 3; PR-IRS, 0), 1 was ER-/PR+ (ER-IRS, 0; PR-IRS, 2), and 1 was ER-/PR- (ER/PR-IRS, 0). Among 9 atrophic endometria from women not treated with Tam, 6 were ER+/PR+ (ER-IRS, 4-12; PR-IRS, 3-6), 1 was ER+/PR- (ER-IRS, 4; PR-IRS, 0), and 2 were ER-/PR- (ER/PR-IRS, 0). The consistent finding of ER and PR expression in endometria from postmenopausal women receiving Tam further supports the suspected estrogenic effect exerted by Tam on endometrial cells. Progestational therapy could be beneficial in the prevention of Tam-induced abnormal endometrial proliferations.     

zALK-8, a novel type I serine/threonine kinase receptor, is expressed throughout early zebrafish development

AIMS: Progressive loss of neuroretinal rim tissue is known to occur early in glaucoma and measurement of the neuroretinal rim area is possible by magnification corrected analysis of optic disc photographs (planimetry). This study was performed to determine whether the facility to distinguish between glaucomatous and normal optic discs could be improved upon by: (a) taking into account the known relation between optic disc size and neuroretinal rim area, and (b) measuring rim area in a number of segments, in order to detect focal changes. METHODS: Planimetric examination of the optic disc photographs of 88 control subjects and 51 patients with early visual field defects was performed. In the control group, multiple linear regression analysis was performed between neuroretinal rim area and optic disc area, age, sex, eye side, refraction, and keratometry. This was repeated for the whole disc and for each of twelve 30 degree segments. Normal ranges were defined by the 98% prediction intervals of the regression analysis and the sensitivity and specificity for correct identification of optic discs in the two groups determined. RESULTS: Multiple linear regression demonstrated significant associations between the neuroretinal rim area and optic disc area and age in normal subjects. Sensitivity and specificity for glaucoma diagnosis, using the cut off derived from the 98% prediction intervals, was 37.7% and 98.9% respectively when total neuroretinal rim area alone was considered, and 88.7% and 94.3% respectively when the 30 degree segments were included. The most frequent pattern of neuroretinal rim loss was diffuse, followed by thinning in more than one sector and then by thinning in the inferotemporal sector alone. CONCLUSIONS: This method of optic disc analysis enables the examiner to identify glaucomatous optic discs at the stage of early perimetric loss with a high degree of precision. Optic disc photography is simple, and fundus cameras are widely available. This method for glaucoma case identification may therefore be suitable for the primary care setting as well as hospital practice.     

Ultrasound backscatter microscope analysis of mouse melanoma progression

The incidence and mortality rate of cutaneous melanoma continue to increase throughout the world, making the study of melanoma biology an important area of current research. While recent breakthroughs in transgenic mouse technology have led to promising mouse skin models of melanoma, there is presently no technique available for quantitatively studying subsurface melanoma progression, in vivo. We demonstrate the first application of an imaging method called ultrasound backscatter microscopy (UBM) for imaging early murine melanomas with spatial resolution of 30 microns axial and 60 microns lateral. Murine B16 F10 melanomas have been imaged from their earliest detection, over several days, until they are 2 to 5 mm in diameter. Melanoma dimensions measured by UBM were found to be in excellent agreement with those determined histopathologically on the excised tumours. The relative rms errors in UBM-determined melanoma height and width were found to be 8.7% and 4.2%, respectively. The mean rate of increase in tumour height of early murine melanoma was found to be 0.37 +/- 0.06 mm/day. Computer-generated volumetric renderings of melanomas have been produced from three-dimensional image data, allowing quantitative comparisons of tumour volumes to be made. Using a priori assumptions of ellipsoid tumour shape, the relative error in UBM-determined volume was shown to be less than 17%. These results should be of considerable interest to investigators studying melanoma biology using mouse skin models, and have implications in the use of high frequency ultrasound imaging for the clinical assessment of cutaneous melanoma.     

Laparoscopic staging and intraoperative ultrasonography for liver tumor management

The histaminergic system is involved in the control of arousal in the brain and may impact significantly on visual processing. However, little is known about the histaminergic innervation of visual areas, or the histamine system in the primate brain, in general. We examined in Macaca mulatta the location of histamine-immunoreactive neurons and the innervation of important cortical and subcortical visual areas by histamine-immunoreactive axons. Brain sections were treated with an antibody to histamine and processed with standard immunohistological procedures. Histamine-immunoreactive neurons (20-45 microns in diameter) were localized bilaterally in the hypothalamus, particularly in ventral, lateral, posterior, and perimammillary hypothalamic areas. These hypothalamic cells appear to provide the sole neural source of histamine in the macaque brain. A plexus of varicose histamine-immunoreactive axons was present throughout the superior colliculus, the dorsal and ventral lateral geniculate nuclei of the thalamus, the reticular nucleus of the thalamus, the lateral posterior/pulvinar complex, and the visual cortex, including areas 17, 18, and the nearby extrastriate cortex. The axons nearly homogeneously innervated every region and layer in these structures, except for an increase in density in layer 1 of the visual cortex and in the superficial-most layers of the superior colliculus. Histaminergic axons broadly innervated every visual region examined. In comparison with the other aminergic and the cholinergic projection systems, which show considerable projection specificity, the histaminergic projection exhibited great homogeneity. The breadth of the distribution of histaminergic axons ensures that virtually all levels of visual processing in the primate can be influenced, either directly or indirectly, by the neuromodulatory effects of histamine.     

Antiestrogen action: differential nuclear retention and extractability of the estrogen receptor

Since there is a much longer uterine nuclear retention of the U-11, 100A (antiestrogen) receptor complex (UARC) than of the estradiol receptor complex (ERC) at 4-12 hrs after injection, experiments were designed to determine if there is a difference between the relative nuclear affinities for the two RCs as determined by extraction with various ionic strength mediums. Although the UARC was retained longer in the nuclear fraction in vivo, the UARC was completely extractable with 0.3M KCl or 50mM spermine, whereas the ERC demonstrates a salt-resistant form. This suggests that the ERC is more tightly bound to nuclear components through this salt-resistant form of the receptor. In addition, various intercalating agents were used to distinguish the different nuclear chromatin DNA sites where the UARC and ERC may be binding. With actinomycin D (50 uM) more ERC than UARC was retained in the nuclear fraction. However, with ethidium bromide (100uM) less ERC than UARC was retained. Also, the ERC selectively released by ethidium bromide is precisely that fraction not released by salt. These results indicate that the UARC and ERC bind to different chromatin loci.