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Overproduction of nitric oxide via inducible nitric oxide synthase (iNOS) is suggested to be a significant pathogenic factor in Helicobacter pylori induced gastritis. The purpose of this study was to examine the role of iNOS in H pylori associated gastric carcinogenesis.Two types of mice were used in this study: iNOS deficient mice (iNOS-/-) and wild-type littermates. Gastric cancer was generated in mice using a combination treatment comprising N-methyl-N-nitrosourea administration and H pylori infection. Fifty weeks after treatment, tumours in gastric tissues from both types of mice were examined using histopathology, immunohistochemistry, and immunoblotting for iNOS and 3-nitrotyrosine.The overall incidence of gastric cancer at week 50 was significantly lower in iNOS-/- compared with iNOS wild-type mice (p0.05). When analysed according to tumour pathology, the incidence of gastric adenocarcinoma was significantly lower in iNOS-/- compared with iNOS wild-type mice (p0.05). Immunostaining for iNOS was clearly observed in adenocarcinoma cells of iNOS wild-type mice, and was characterised by a strong cytoplasmic expression pattern. 3-Nitrotyrosine was expressed mostly in the area of the lamina propria of gastritis and adenoma lesions in iNOS wild-type mice. Immunoblotting analyses showed that iNOS and 3-nitrotyrosine were also expressed in both adenoma and adenocarcinoma tissues from iNOS wild-type mice. iNOS and 3-nitrotyrosine expression was greater in tumour tissues than in non-tumour tissues.These findings suggest that iNOS contributes to H pylori associated gastric carcinogenesis in mice.

1. This study investigated the effects of dietary supplementation with chromium picolinate on the performance, serum and carcase traits and lipid metabolism of broilers. In trial 1, 120 1-day-old broilers with an equal number of males and females were assigned at random to 4 groups with 3 replicates. Four treatments with dietary supplements of 0 (control), 800, 1600 and 3200 microg/kg of chromium picolinate were used. In trial 2, 6-week-old broilers (20) were used to determine how supplements of 0, 200, 400 and 800 microg/kg chromium in an incubation medium influence their hepatocyte lipogenic capacity and adipocyte lipolysis, in vitro. 2. Dietary supplements of 1600 and 3200 microg/kg chromium in broiler diets significantly increased food consumption (P0.05); 1600 microg/kg markedly improved weight gain (P0.05); 1600 and 3200 microg/kg groups showed increased liver lipid content (P0.05). However, the abdominal fat content tended to decrease in these 2 groups. 3. Dietary supplements of 1600 and 3200 microg/kg of chromium decreased serum glucose and nonesterified fatty acids (NEFA) concentrations while increasing serum phospholipid content (P0.05). Insulin concentration decreased only in birds receiving 3200 ppb chromium (P0.05). Serum triacylglycerol (TG) clearance rate in chromium-supplemented groups was markedly enhanced (P0.05). 4. In addition, chromium supplemented groups had increased serum HDL contents and also reduced serum VLDL and LDL contents (P0.05). 5. Trial 2 indicated that lipogenesis from [U-14C]glucose by isolated hepatocytes was significantly enhanced by 400 ppb chromium (P0.05). 6. The results from this study demonstrate that a supplement of 1600 microg/kg of chromium picolinate in the ration influences the growth, carcase, serum traits and lipid metabolism of broilers.

Parathyroid hormone-related protein (PTHrP) is expressed by malignant tumors and leads to the syndrome of humoral hypercalcemia of malignancy. It is also expressed by a wide variety of nonmalignant tissues, in which it appears to play distinct paracrine and/or autocrine roles. The human PTHrP gene encodes three cDNA-predicted initial translational products of 139, 141, and 173 amino acids. Most human cell lines contain mRNAs encoding all three PTHrP isoforms. The physiological rationale for the existence of these three highly similar transcripts is unknown. In order to determine whether the protein products derived from these three transcripts differ, we transfected Chinese hamster ovary (CHO) cells and rat insulinoma (RIN) cells individually with cDNAs encoding human PTHrP( 1-139), PTHrP( 1-141), and PTHrP( 1-1 73). Cell extracts and conditioned medium were then chromatographed using reversed- phase HPLC and analyzed using region-specific PTHrP immunoassays. As we had previously observed in SKRC-1 (renal cell carcinoma) and RIN( 1-141) cells, multiple amino-terminal PTHrP species as well as a separate midregion PTHrP species were identified in all six cell lines. In addition, both CHO and RIN cell lines transfected with the PTHrP( 1-1 39) construct contained a previously unrecognized carboxy- terminal fragment that reacted with a PTHrP( 109-1 38) antiserum. This carboxy-terminal fragment was physically distinct from the midregion fragment discovered earlier and was also present in conditioned medium, indicating that it is a secretory form, rather than a biosynthetic intermediate or a degradation product. Surprisingly, RIN and CHO cells transfected with PTHrP( 1-141) or -( 1-173) contained little of this carboxy-terminal fragment, suggesting that isoform-specific protein processing exists for PTHrP. In addition, while RIN cells produced a single predominant amino-terminal species, CHO cells contained two, approximately equimolar, amino-terminal species, indicating the existence of cell-specific protein processing. These studies indicate that the posttranslational processing of PTHrP is highly complex. Specifically, (a) multiple amino-terminal PTHrP secretory forms, as well as a midregion form, are generated by cell lines containing each of the three PTHrP transcripts; (b) the Arg3' cleavage that generates the midregion fragment occurs in the Golgi apparatus, as both constitutive and regulated secretory cell types are capable of performing this cleavage; (c) a previously unrecognized carboxy-terminal fragment of PTHrP is secreted; and (d) processing of PTHrP appears to be both isoform- and cell-specific. Complete structural determination of each of these fragments is critical to understanding PTHrP physiology and pathophysiology. Parathyroid hormone-related protein (PTHrP) was orig- inally isolated from human cancers associated with the syndrome of humoral hypercalcemia of malignancy (HHM) (Bilezikian, 1990; Broadus & Stewart, 1994; Halloran & Nissenson, 1992; Stewart & Broadus, 1990a,b; Strewler & Nissenson, 1990). Since then, the presence of either PTHrP protein, mRNA, or both has been documented in a multitude of normal, non-malignant human and animal tissues (Bilez- ikian, 1990; Broadus & Stewart, 1994; Halloran & Nissenson, 1992; Stewart & Broadus, 1990a,b; Strewler & Nissenson, 1990). These include sites as diverse as lactating breast, pituitary, placenta, bone, uterus, CNS, and epidermis, as well

Low-back pain has a complex and multi-faceted etiology. The articular facets have been shown to be load-bearing structures and may be a site for low-back pain. The aim of this paper is to establish the mechanism for the transmission of axial load across a facet joint and to propose a facet-related hypothesis for low-back pain. The mechanism of load transmission was studied by two methods. Lumbar segments were instrumented with an intervertebral load cell (IVLC) to measure disc load so that facet load could be deduced. The applied load was moved 10 mm anteriorly and 12.5 mm posteriorly from the center of the vertebral body. The facets then were separated from the body and loaded axially to determine their stiffness in tension and compression and to observe the failure mode of the joint. It was shown optically that compressive loading of the isolated facet joints was equivalent to spinal extension and tensile loading to spinal flexion. Lastly, a finite element model of a lumbar motion segment was developed to simulate the transmission of facet load and to study the effects of disc degeneration on facet loads. Results of the study on six lumbar segments revealed that the normal facets carried 3-25%. If the facet joint was arthritic, the load could be as high as 47%. Experiments on isolated facet joints revealed that they behaved as a stiffening spring in compression and were weak in tension.(ABSTRACT TRUNCATED AT 250 WORDS)