Immunohistochemical localization of hepatic nitric oxide synthase in normal and transgenic sickle cell mice: the effect of hypoxia

Nitric oxide (NO) generated from L-arginine and molecular oxygen by nitric oxide synthase (NOS) has been shown to influence hepatocellular function and pathology in response to ischemia and certain hepatotoxins. In the present study, we examined the liver of a transgenic line of sickle cell mice for hepatocellular injury and localization of two isoforms of NOS, the endothelial constitutively expressed isoform (EcNOS) and the inducible isoform (iNOS) by immunohistochemistry. Diffuse expression of EcNOS was observed in hepatocytes of control and sickle cell animals maintained under room air conditions. In contrast, iNOS was observed only in the sickle cell mice, well-localized to hepatocytes surrounding the central veins of the lobules. When normal mice were exposed to hypoxic conditions for 4 to 5 days, iNOS immunostaining appeared de novo in a patchy distribution throughout the liver lobules. In the sickle cell mice, hypoxia appeared to increase the subjective intensity of pericentral staining of iNOS. Liver histology was normal in the sickle cell mice maintained under room air conditions, but showed multifocal areas of necrosis when sickling was exacerbated by chronic hypoxic conditions. However, a pericentral zone of preserved architecture was present, corresponding to the region of iNOS staining. We postulate that pericentral induction of iNOS under ambient conditions occurs in transgenic sickle cell mice in response to particularly intense hypoxic conditions near the central veins of the liver. Increases in NO synthesis may occur in this region, which would serve to protect these cells from ischemic damage either directly or by maintaining blood flow. These findings could be relevant to liver pathophysiology in patients with sickle cell disease.     

The relationship between PGE2 level in mothers' milk and physiological diarrhea of the baby and the treatment

Physiological diarrhea of baby during the period of breastfeeding often occurs. To investigate the relationship between mother's milk and the physiological diarrhea of baby, we measured the PGE2 levels in milk of 320 lactating women within 4 months of postpartum with radioimmunoassay and the mean value of PGE2 level was 216.8 +/- 145.2 ng/L. The PGE2 levels in mother's milk in the group with diarrhea were 286.5 +/- 142.2 ng/L, that of control group 130.4 +/- 76.3 ng/L. The difference was obviously significant (P < 0.001). The physiological diarrhea of baby was positively related to the PGE2 level in mother's milk (r = 0.75, P < 0.01) i.e., the high PGE2 level in mother's milk may be an important cause of diseases. The observation on 102 cases of baby with severe physiological diarrhea showed a higher level of PGE2 in the mother's milk. 52 cases of lactating women in the treated group were given indomethacin, and after treatment the PGE2 level in mother's milk decreased obviously, and the diarrhea of baby disappeared. The effective rate was 96.15%. No side effects were found in both mother and baby.     

Characterization of glucuronic acid conjugates of a novel angiotensin receptor antagonist

Nanogram quantities of glucuronic acid conjugates of GR117289 in rat and dog bile have been analysed by semi-microbore high-performance liquid chromatography (HPLC)/ionspray mass spectrometry with on-line UV diode array detection. The determination of drug metabolites in bile has often proved problematical due to the large number of endogenous components in this biological matrix, in particular the bile acids. Semi-microbore HPLC is useful for concentrating small quantities of material and, in combination with an on-line diode array detector, for distinguishing between drug related and endogenous components. A novel angiotensin II receptor antagonist, GR117289, had proved difficult to analyse by thermospray mass spectrometry because of its thermal lability. The use of the less thermally dependent technique of ionspray mass spectrometry allowed the characterization of nanogram quantities of glucuronic acid metabolites of GR117289 in bile.     

Role of the nuclear localization sequence in fibroblast growth factor-1-stimulated mitogenic pathways

Fibroblast growth factor-1 (FGF-1) is a potent mitogen for mesoderm- and neuroectoderm-derived cell types in vitro. However, a mutant FGF-1 with deletion in its nuclear localization sequence (NLS, residues 21-27) is not mitogenic in vitro. We demonstrated that synthetic peptides containing this NLS were able to stimulate DNA synthesis in a FGF receptor-independent manner after they were delivered into living NIH 3T3 cells by a cell-permeable peptide import technique. The stimulation of maximal DNA synthesis by these peptides required the presence of peptides during the entire G1 phase of the cell cycle. The mitogenic effect was specific for the NLS of FGF-1 because a peptide with double point mutations at lysine residues was inactive in stimulating DNA synthesis. Our results suggest that the NLS plays an important role in the mitogenic pathway initiated by exogenous FGF-1 by its direct involvement in the nuclear transport and signaling of internalized FGF-1.     

An new index to evaluate the elderly health care-geracomia effect index

This paper introduced a new index--geracomia effect index (GEI) which is expressed by the ratio of survival years of the elderly after their retirement to the expected survival years in order to evaluate the health care service to the elderly. The application of this index was discussed using the mortality data of cardiovascular diseases of a city from 1983 to 1994. The results showed that coronary heart disease, pulmonary heart disease and cerebrovascular disease had a stable influence on the survival years of the elderly during this period while the negative effect of diabetes had been weaken with the calendar years. However, myocardial infarction had begun to threaten the younger groups. The author realized that it needs further practice to make the index applicable.     

The glucose-dependent transactivation activity of ABF1 on the expression of the TDH3 gene in yeast

We used titanium anchors for the surgical repair of rotator cuff tears in 34 selected patients, all of whom were < 60 years of age, had good bone quality, and had no known metabolic bone diseases. Nine tears were repaired within 6 months, 15 within 6-12 months, and 10 later than 12 months after injury. Tear size was graded as small (10 patients), medium (15 patients), and large (nine patients) during open operation. After 6-24 months of follow-up, 30 patients reported satisfactory pain relief, function, active forward flexion, and muscle strength [18 excellent and 12 good results based on the University of California at Los Angeles rating system (UCLA scores)]; there were no implant failures (p < 0.001). Two patients had unsatisfactory function but good relief of pain, whereas two patients were dissatisfied with their overall result (four poor results based on UCLA scores). Although trans-bone suturing is presently the most common and successful surgical technique for rotator cuff tears, we found that use of titanium anchors shortens operative time and has results comparable with the traditional technique. Titanium anchors should not be used when bone quality is poor or good patient compliance is doubtful. They are also contraindicated, as our four poor results indicate, when the tear is old (> 6 months) and large (diameter > 5 cm with significant tissue degeneration).     

A natural vaccine candidate strain against cholera

E1 Tor Vibrio cholerae (EVC) strains may be classified into two kinds-epidemigenic (EEVC) strains and non-epidemigenic (NEEVC) strains-based on a phage-biotyping system. A large number of EEVC strains have been screened for toxigenic and putative colonization attributes. One such naturally occurring strains (designated IEM101) has been found which is devoid of genes encoding cholera toxin (CT), accessory cholera enterotoxin (ACE), zonula occludens toxin (ZOT), but possesses RS1 sequences and toxin-coregulated pilus A gene (icpA) although icpA is poorly expressed. It expresses type B pili but does not possess type C pili. It is an E1 Tor Ogawa strain and does not cause fluid accumulation in rabbit ilcal loop tests. Active immunization of rabbits with strain IEM101 elicited good protection against challenge with virulent strains of V. cholerae O1. Oral administration caused no side effects in 15 human volunteers, colonized the gut for four to ten days and elicited good immune responses.