Biomedical subjects

Y Kawai

Publications and source records attributed to Y Kawai.

At least 91 records · Page 5Linked to original sources

PubMed1999

1,25-Dihydroxyvitamin D3 induces differentiation of a retinoic acid-resistant acute promyelocytic leukemia cell line (UF-1) associated with expression of p21(WAF1/CIP1) and p27(KIP1).

Retinoic acid (RA) resistance is a serious problem for patients with acute promyelocytic leukemia (APL) who are receiving all-trans RA. However, the mechanisms and strategies to overcome RA resistance by APL cells are still unclear. The biologic effects of RA are mediated by two distinct families of transcriptional factors: RA receptors (RARs) and retinoid X receptors (RXRs). RXRs heterodimerize with 1, 25-dihydroxyvitamin D3 [1,25(OH)2D3] receptor (VDR), enabling their efficient transcriptional activation. The cyclin-dependent kinase (cdk) inhibitor p21(WAF1/CIP1) has a vitamin D3-responsive element (VDRE) in its promoter, and 1,25(OH)2D3 enhances the expression of p21(WAF1/CIP1) and induces differentiation of selected myeloid leukemic cell lines. We have recently established a novel APL cell line (UF-1) with features of RA resistance. 1,25(OH)2D3 can induce growth inhibition and G1 arrest of UF-1 cells, resulting in differentiation of these cells toward granulocytes. This 1, 25(OH)2D3-induced G1 arrest is enhanced by all-trans RA. Also, 1, 25(OH)2D3 (10(-10) to 10(-7) mol/L) in combination with RA markedly inhibits cellular proliferation in a dose- and time-dependent manner. Associated with these findings, the levels of p21(WAF1/CIP1) and p27(KIP1) mRNA and protein increased in these cells. Northern blot analysis showed that p21(WAF1/CIP1) and p27(KIP1) mRNA and protein increased in these cells. Northern blot analysis showed that p21(WAF1/CIP1) and p27(KIP1) transcripts were induced after 6 hours' exposure to 1,25(OH)2D3 and then decreased to basal levels over 48 hours. Western blot experiments showed that p21(WAF1/CIP1) protein levels increased and became detectable after 12 hours of 1,25(OH)2D3 treatment and induction of p27(KIP1) protein was much more gradual and sustained in UF-1 cells. Interestingly, the combination of 1, 25(OH)2D3 and RA markedly enhanced the levels of p27(KIP1) transcript and protein as compared with levels induced by 1, 25(OH)2D3 alone. In addition, exogenous p27(KIP1) expression can enhance the level of CD11b antigen in myeloid leukemic cells. In contrast, RA alone can induce G1 arrest of UF-1 cells; however, it did not result in an increase of p21(WAF1/CIP1) and p27(KIP1) transcript and protein expression in RA-resistant cells. Taken together, we conclude that 1,25(OH)2D3 induces increased expression of cdk inhibitors, which mediates a G1 arrest, and this may be associated with differentiation of RA-resistant UF-1 cells toward mature granulocytes.

Calcitriol↗

PubMed1999

Leukemia inhibitory factor, glial cell line-derived neurotrophic factor, and their receptor expressions following muscle crush injury.

Using in situ hybridization histochemistry, we characterized the spatiotemporal gene expression patterns of leukemia inhibitory factor (LIF) and glial cell line-derived neurotrophic factor (GDNF), and their receptor components (LIFR, GFR-alpha1, RET) induced in muscle cells, intramuscular nerves, and motoneurons in the regeneration processes of both muscle cells and nerves following muscle contusion. Muscle contusion induced upregulation of GDNF and GFR-alpha1 mRNAs in Schwann cell-like cells in the intramuscular nerves and of LIFR mRNA in damaged muscle cells. LIFR, GFR-alpha1, and RET mRNA expressions in motoneurons were upregulated following muscle contusion. Muscle contusion also induced more rapid, prominent transactivations of GFR-alpha1 and RET genes in motoneurons than did sciatic nerve axotomy. These findings suggest that rapid and prominent upregulation of the receptor components for LIF and GDNF in motoneurons is important for the regeneration of intramuscular motor nerves damaged by muscle contusion.

Animals↗

PubMed1999

Right hepatic lobectomy for hepatocellular carcinoma which developed in primary biliary cirrhosis: report of a case.

The case of a 74-year-old female patient who underwent a right hepatic lobectomy for hepatocellular carcinoma (HCC) which developed in primary biliary cirrhosis (PBC) is reported herein. During a follow-up examination for Parkinson's disease, an elevation of hepatobiliary tract-related enzymes and alpha-fetoprotein was uncovered. Diagnostic imagings showed a hypervascular, solitary, and encapsulated tumor measuring about 7 cm in diameter located mainly in the posterior segment. Positive antimitochondrial and antinuclear antibodies and a preoperative liver biopsy strongly suggested well differentiated HCC developed in PBC (Scheuer's classification stage II). Since the natural prognosis of PBC estimated by the Mayo risk score was fairly good and the liver function indicated sufficient tolerance for major hepatic resection, and preoperative computed tomography (CT) volumetry showed the atrophy of the right hepatic lobe, a right hepatic lobectomy was performed. A pathological examination revealed well encapsulated, moderately differentiated HCC with, in part, well-differentiated HCC in the tumor and stage II PBC in the noncancerous region. CT volumetry performed at postoperative day 14 showed a 146% enlargement of the remnant liver. An early detection of HCC and PBC by strict screening would prevent a limitation of surgical therapy due to a deteriorated liver function.

Aged↗

PubMed1999

Hepatocyte growth inhibitory factor derived from HTLV-I(+) T-cell line is identical to IL-6.

We previously reported that the culture supernatant of the human T-cell leukemia virus (HTLV-I) infected-T-cell line--ATL-2--included factor(s), which had an inhibitory effect on epidermal growth factor (EGF)-stimulated proliferation of primary cultured rat hepatocytes. After crude purification, we arbitrarily named it hepatocyte growth inhibitory factor (HGI). In this study, we further purified HGI and determined its amino acid sequence. For purification, we used 4-steps column chromatography and SDS-PAGE. The purified proteins consisted of two bands of 20 and 27 kDa in SDS-PAGE analysis. Protein extracted from each band had an inhibitory effect on rat hepatocyte growth. Amino acid analysis of the purified 20 kDa band revealed that the 34 amino acids were identical to those of IL-6. The inhibitory effect of the factor was neutralized by an anti IL-6 neutralizing antibody. Using Western blot analysis of HGI, an anti IL-6 antibody recognized both 20 and 27 kDa bands. Consequently HGI was determined to be identical to IL-6, which occurred in higher levels in the sera of adult T-cell leukemia (ATL) patients.

Aged↗

PubMed1999

Rabbit P300-like potential depends on cortical muscarinic receptor activation.

Novel stimuli trigger a positive brain potential P300 or P3a in mammalian animals, which is considered to represent an orienting response. Drugs systemically administered showed that acetylcholine is involved in the generation of P3. However, it is not known in which structure acetylcholine interacts with other neuronal substances for P3 generation. In this study, we injected scopolamine, an acetylcholine antagonist, into the parietal cortex. After the injection the amplitude of P3 from the parietal electrode decreased, while P3 recorded from neighbouring cortex was preserved. The peak latency of it did not show any significant change after the injection. P3 did not show any significant change after injecting normal saline into the same area. The parietal cortex is an essential structure for local P3 generation Different cerebral cortical regions respond to novel stimuli in parallel, and muscarinic receptor activation is necessary for processing the information of novelty detection.

Acoustic Stimulation↗

PubMed1999

Electrophysiological and morphological characterization of cytochemically-defined neurons in the caudal nucleus of tractus solitarius of the rat.

Morphological and electrophysiological properties of calbindin D-28k-, GABA- and dopamine-beta-hydroxylase-immunopositive neurons were investigated in the caudal nucleus of tractus solitarius of rats, using a patch-clamp whole-cell recording combined with intracellular staining and immunocytochemistry. Calbindin D-28K- and GABA-positive neurons had a small cell body (10.9+/-0.3 microm in diameter) and were distributed throughout the caudal nucleus of tractus solitarius. Double fluorescence immunocytochemistry revealed that calbindin- and GABA-positive neurons formed distinct subpopulations. Calbindin- and GABA-positive neurons double stained for biocytin showed extensive axon collaterals within the nucleus of tractus solitarius and some calbindin-positive, but not GABA-positive neurons, had also projection axons leaving the nucleus of tractus solitarius. Dopamine-beta-hydroxylase-immunopositive neurons had a small (10.8+/-0.3 microm) or large (17.2+/-0.4 microm) cell body. Neurons with a small cell body were observed in the dorsomedial nucleus at the level of the area postrema, and in the area postrema, while neurons with a large cell body were observed in the medial nucleus throughout the caudal nucleus of tractus solitarius. Double fluorescence immunocytochemistry revealed that almost all small dopamine-beta-hydroxylase-positive neurons were also immunoreactive for calbindin, while large dopamine-beta-hydroxylase-positive neurons were not. Double staining for dopamine-beta-hydroxylase and biocytin showed that neurons with a small cell body had moderate axon collaterals. On the contrary, neurons with a large cell body had few, if any, axon collaterals and a projection axon which could leave the nucleus of tractus solitarius. Following stimulation of the tractus solitarius, all neurons with a small cell body exhibited a polysynaptic excitatory response (type I neurons), while dopamine-beta-hydroxylase-immunopositive neurons with a large cell body exhibited a monosynaptic excitatory response (type II neurons) or an excitatory followed by an inhibitory response (type III neurons). Spontaneous and evoked excitatory postsynaptic currents of (type I neurons) calbindin- or GABA-positive neurons were reversibly blocked by 6-cyano-7-nitroquinoxaline-2,3-dione. Spontaneous and evoked inhibitory postsynaptic currents of type III neurons were reversibly blocked by bicuculline. Type II neurons showed no spontaneous excitatory nor inhibitory postsynaptic currents. It was concluded that the three kinds of chemically-defined neurons formed distinct neuronal subpopulations in the caudal nucleus of tractus solitarius in terms of synaptic responses and morphological characteristics such as cell size and axonal trajectory.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1999

Chemical characterisation of six oligosaccharides in a sample of colostrum of the brown capuchin, Cebus apella (Cebidae: primates).

Carbohydrates were extracted from a sample of brown capuchin colostrum and six of the component oligosaccharides were separated and purified by gel filtration and preparative thin layer chromatography. Their structures were determined by 1H-NMR to be as follows: Gal beta 1-->4[Fuc alpha 1-->3]Glc (3-fucosyllactose) Gal beta 1-->3Gal beta 1-->4Glc (beta-3'-galactosyllactose) Gal beta 1-->6Gal beta1-->4Glc (beta-6'-galactosyllactose) Gal beta-->3[Gal beta 1-->4GlcNAc beta 1-->6]Gal beta 1-->4Glc (lacto-N-novopentaose I) Gal beta 1-->4GlcNAc beta 1-->3[Gal beta 1-->4GlcNAc beta 1-->6]Gal beta 1-->4Glc (lacto-N-neohexaose) Neu5Ac alpha 2-->3Gal beta 1-->4Glc (3'-N-acetylneuraminyllactose) Of these, all except lacto-N-novopentaose I have been previously found in human milk or colostrum.

Animals↗

PubMed1999

Protective effects of some flavonoids on the renal cellular membrane.

By assaying lactate dehydrogenase and malondialdehyde leakage from LLC-PK1 cells in culture, a study was conducted to clarify whether flavonoid compounds ameliorate renal cellular injury. The cells were cultured with various concentrations of samples under routine conditions. The results demonstrated that baicalin, cirsimaritin, 6-hydroxyluteolin, luteolin, plantaginin, rhoifolin, sorbarin, afzelin, hyperin, isoquercitrin, isorhamnetin, kaempferitrin, kaempferol-7-glucoside, oxyayanin A, quercetin, quercitrin, rhamnetin and rutin exerted marked protective effects on the cells, whereas acacetin, apigenin, apiin, cirsilineol, genkwanin, pectolinarin and tetramethylquercitin had virtually no effect. In the light of these findings, we propose that the general capability of these compounds is largely decided by the number and position of phenolic hydroxyl groups linked to the structural backbone.

Animals↗

PubMed1999

Peripheral blood stem cell collection and transplantation using the Haemonetics Multi Component System.

AIM: To assess clinical usefulness of an intermittent-flow blood cell separator in peripheral blood stem cell (PBSC) collection and transplantation. RESULTS: The Haemonetics Multi Component System (Multi) was used to collect PBSC (52 aphereses in 17 patients). The mean processing blood volume and the mean PBSC yield were 7407 ml and 2.16 x 10(6) CD34+ cells/kg, respectively. When CD34+ cells exceeded 0.3% of the peripheral WBC, more than 2.0 x 10(6) CD34+ cells/kg could be collected by a single apheresis. Eight patients underwent PBSC transplantation after high-dose chemotherapy. Hematopoietic recovery was achieved in a median period of 10 days. CONCLUSIONS: (1) A single-arm, light-weight machine has sufficient capability to collect PBSC. (2) The percentage of CD34+ cells in the peripheral WBC is a good predictor of the CD34+ cell yield of the collection.

Adult↗

PubMed1999

Detection of mRNA species in bulbospinal neurons isolated from the rostral ventrolateral medulla using single-cell RT-PCR.

The rostral ventrolateral medulla (RVL) contains neurons which are critically involved in the tonic and reflex control of blood pressure. Some of these neurons project to the intermediolateral cell column of the thoracolumbar spinal cord and excite preganglionic sympathetic neurons. In order to gain a better understanding of the properties of the RVL neurons at the cellular and molecular level, a protocol was developed utilizing acute dissociation and the reverse transcription-polymerase chain reaction (RT-PCR) to study the expression of several genes in single RVL neurons. Neurons were dissociated from the RVL region of young rats, and classified as spinally projecting or non-spinal by the presence or absence of retrogradely transported fluorescent beads injected into the upper thoracic segments of the spinal cord. Individual neurons were collected by aspiration into a glass micropipette and analysed by RT-PCR. The presence of either glyceraldehyde 3-phosphate dehydrogenase (GAPDH) or neuron-specific enolase (NSE) mRNA was used as the criterion for selecting cells for further analysis. A subpopulation (50%) of spinally projecting, GAPDH- or NSE-positive neurons expressed mRNA for tyrosine hydroxylase (TH) or phenylethanolamine N-methyltransferase (PNMT), indicative of catecholaminergic or C1 adrenergic neurons, respectively. Some bulbospinal RVL neurons, including those that were TH- or PNMT-positive, were also found to express mRNA for the mineralocorticoid receptor (MR), the glucocorticoid receptor (GR), noradrenaline transporter (NET), and neuronal glutamate transporter (EAAC1). The glial glutamate transporter (GLT), glycine transporter (GLYT2), glutamic acid decarboxylase (GAD67) and gamma-amino butyric acid (GABA) transporter (GAT-1) were not expressed. The single-cell RT-PCR protocol is a powerful, yet simple and relatively rapid method for analysis of mRNA expression in a defined neuronal population. It can be combined with whole-cell patch-clamp recording prior to RT-PCR analysis, allowing linkage of the molecular analysis of mRNA expression to the electrophysiological and pharmacological properties of single neurons. The method is very sensitive, enabling mRNA transcripts in low abundance to be detected, and its application in our recent studies provided novel information about neurons involved in blood-pressure regulation at the molecular and cellular level.

Animals↗

PubMed1999

Future aspects of BMIPP.

Iodinated fatty acid compounds have an important role in early detection of myocardial abnormalities and provide insights into pathological states in the heart. Among them, 15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid (BMIPP) has been most widely used providing excellent images of the left ventricular myocardium due to high myocardial uptake and long retention. The previous chapters have focused on the basic characters and clinical applications of this compound. However, the precise mechanisms of myocardial kinetics should be further investigated under various conditions. Most of the studies showed reduced BMIPP uptake relative to perfusion in a variety of myocardial disorders, whereas an increase in BMIPP uptake relative to perfusion is often reported. The potential mechanisms of such conflicting results are discussed, but basic studies should be performed to clarify such results in detail. There are a number of clinical values of this compound. Since alteration of fatty acid is observed in the repetitive ischemia, BMIPP can be used for detecting severe ischemic episodes. The concept of 'ischemic memory' imaging can be applied for patients with unstable or vasospastic angina at rest and for those with acute myocardial infarction with successful revascularization to identify the risk area. The discordant decrease in BMIPP uptake relative to perfusion is often seen in ischemic but viable myocardium, and therefore, the combined imaging of BMIPP and perfusion can be used for assessment of tissue viability. Furthermore, abnormal BMIPP uptake is most often observed in hypertrophic cardiomyopathy, and thus, this compound can be used for an early detection and differential diagnosis of the cardiomyopathy. Although BMIPP imaging seems to be quite promising in many fields, the number of patient data remain limited. In this respect, a multicenter study with a vast majority of patients is warranted to confirm these important values of BMIPP. In addition, this attractive tracer should be available all over the world to confirm its clinical value in the near future.

Cardiomyopathies↗

PubMed1999

Sulfated sialic acid-polymers inhibit the cytotoxic action of bee and snake venom.

Colominic acid is an alpha2,8-linked sialic acid polymer produced by Escherichia coli. We found that synthetic sulfated-colominic acids (SC) remarkably inhibited the cytotoxicity of bee and snake venom toward mouse fibroblast cells, but colominic acids showed no inhibition themselves, indicating the important role of sulfate groups in the inhibitory activity of SC. Other sulfated carbohydrates such as chondroitin sulfates, heparin and heparan sulfate showed no inhibition. SC also exhibited potent inhibition of melittin, a highly basic peptide, which is a major cytotoxic component of bee venom. SC did not inhibit phospholipase A2 activity in bee venom. This suggests that the inhibition of bee and snake venom by SC is due to inhibition of melittin and cardiotoxin, which is a cytolytic peptide in snake venom, respectively. SC with a higher sulfur content and a larger molecular mass showed more potent activity. The interaction between SC and melittin basically seems an ionic one, however, the conformation of SC is also likely important. For the binding of SC to melittin leading loss of its cytotoxic activity, the sulfate groups of SC must be properly arranged to interact with lysine and arginine residues of melittin molecules, which play an important role in the cytolytic activity. A higher molecular mass of SC substituted with more sulfate groups is required for more obvious inhibition of the cytotoxic activity.

Animals↗

PubMed1999

The effect of selective cyclooxygenase-2 inhibitor on corneal angiogenesis in the rat.

PURPOSE: Eicosanoids that are present in inflamed tissues are thought to play a significant role in angiogenesis. Cyclooxygenase, a key enzyme in eicosanoid synthesis, has recently been shown to exist in two isoforms: the constitutive COX-1 and the inducible COX-2. This study was undertaken to determine the role of COX-2 in the corneal angiogenic response. METHODS: Angiogenesis in the rat cornea was provoked by chemical cautery. Either NS-398, a selective COX-2 inhibitor, or indomethacin, a non-selective COX inhibitor, was applied topically 3 times daily for 4 days. Neovascularization was quantitated by digital image analysis in corneal flat preparations. To test their inhibitory effects on eicosanoid synthesis, normal or cauterized corneas were incubated in the culture medium with the inhibitor. Prostaglandin E2 in the medium was assayed using an enzyme-linked immunosorbent assay. RESULTS: Both NS-398 and indomethacin significantly inhibited corneal neovascularization with the % inhibition of 36.4 +/- 9.6%, and 38.5 +/- 9.0%, respectively, when applied topically at a concentration of 0.1% (p <.001). Neither reduced the angiogenic response at a concentration of 0.01% or below. PGE(2) production in the cauterized cornea was 2.0 times higher than that in the controls. In normal corneas, indomethacin inhibited PGE(2) synthesis by 80%, whereas NS-398 inhibited it by no more than 20%. In contrast, in injured corneas, both indomethacin and NS-398 inhibited PGE(2) synthesis in a similar fashion, with a maximal inhibition rate of 75 to 80%. CONCLUSIONS: Our results suggest that COX-2 induction in cauterized corneas increases the level of eicosanoids, which result in corneal angiogenesis.

Administration, Topical↗

PubMed1999

Dietary defatted sesame flour decreases susceptibility to oxidative stress in hypercholesterolemic rabbits.

Plant glucosides possess antioxidative properties due to their ability to scavenge free radicals. Sesame seeds contain a class of these compounds, the sesaminol glucosides. To evaluate their antioxidative activity in vivo, we fed rabbits diets containing 1% cholesterol (Chol) with or without 10% defatted sesame flour (DSF) (containing 1% sesaminol glucosides) for 90 d. We determined the susceptibility of their tissues to oxidation ex vivo as well as serum total cholesterol (TC), phospholipid (PL), triglyceride (TG) and HDL cholesterol (HDL-C) concentrations. Serum TC, HDL-C, PL and TG levels were unaffected by the addition of DSF. The HDL-C in the Chol + DSF group was greater than in the Chol group at 45 d. Both were greater than in the groups that did not consume cholesterol. Liver TC and TG were significantly lower in rabbits fed the diet containing DSF plus 1% cholesterol than in those fed 1% cholesterol alone. Lipid peroxidation activity, measured as 2-thiobarbituric acid reactive substances (TBARS), was lower in the liver (P < 0.05) and serum (P = 0.06) of rabbits fed DSF plus cholesterol than in rabbits fed the cholesterol diet. Although we did not detect sesaminol glucosides in peripheral tissues, we observed abundant quantities of sesaminol in rabbits fed DSF, the principal metabolite. Our findings suggest that feeding DSF to rabbits does not protect cholesterol-induced hypercholesterolemia, but may decrease susceptibility to oxidative stress in rabbits fed cholesterol, perhaps due to the antioxidative activity of sesaminol.

Analysis of Variance↗

PubMed1999

Formation of the aldehydic choline glycerophospholipids in human red blood cell membrane peroxidized with an azo initiator.

The production of phospholipid hydroperoxide and aldehydic phospholipid was examined in human red blood cell (RBC) membranes after peroxidation with 2,2-azobis(2-amidinopropane)dihydrochloride (AAPH) or xanthine/xanthine oxidase (XO/XOD/Fe3+). Both radical-generation systems caused a profound decrease in the amount of polyunsaturated fatty acid (PUFA) in choline glycerophospholipid (CGP) and induced formation of peroxidized CGP in RBC membranes to different extents. No consistent generation of peroxidized lipids from CGP was evident after peroxidation with XO/XOD/Fe3+, which caused the apparent decomposition of phospholipids and the formation of large amounts of thiobarbituric acid-reactive substance (TBARS). On the other hand, CGP hydroperoxide was formed as a primary product of peroxidation with AAPH. Aldehydic CGP was also detected as a secondary product of hydroperoxide decomposition in AAPH-peroxidized RBC membranes. Aldehydic CGP was preferentially generated from arachidonoyl CGP rather than from linoleoyl CGP in AAPH-peroxidized membranes. AAPH mainly oxidized CGP to hydroperoxide and aldehydic phospholipids. The sum of hydroperoxide and aldehyde of CGP corresponded to the loss of CGP due to peroxidation by AAPH. This result indicates that CGP was mainly converted into these two oxidized phospholipids in AAPH-peroxidized RBC membranes.

Aldehydes↗

PubMed1999

Biomechanical properties and chemical composition of the aorta in genetic hypertensive rats.

OBJECTIVE: To study the alteration in the biomechanical properties of the thoracic aorta and its composition in young normotensive Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP). METHODS: The in-vitro biomechanical properties of the aorta in 4- and 12-week-old SHRSP were determined by means of a tensile testing machine and compared with those of the SHR and WKY rats; in addition, a biochemical analysis of collagen, elastin and advanced glycation endproducts was performed. RESULTS: The aortic biomechanical properties were altered in the 4- and 12-week-old SHRSP, compared with age-matched WKY rats and SHR. The maximum stress in the 12-week-old SHRSP was reduced by 27% compared with the normotensive WKY rats, and by 26% compared with the SHR. The maximum strain values in the 4- and 12-week-old SHRSP were lower than those in the age-matched WKY rats, by 12 and 9% respectively, whereas this value in the 12-week-old SHR was significantly increased (by 26%) compared with the age-matched WKY rats. No differences were observed in the aortic contents of collagen and elastin between the SHRSP and SHR. However, the extractability of collagen by pepsin digestion in the 12-week-old SHRSP was lower than that in the age-matched SHR and WKY rats, and a significantly larger accumulation of advanced glycation endproducts was observed in the 12-week-old SHRSP than in the age-matched SHR and WKY rats, suggesting a greater formation of collagen-derived cross-links in SHRSP. CONCLUSIONS: From these results, we conclude that decreased aortic distensibility and mechanical strength values are partly related to the greater formation of collagen-derived cross-links in 12-week-old SHRSP, and that the mechanical properties in SHRSP may be the result not only of the larger formation of collagen-derived cross-links but also of primary defects, since the aortic mechanical strength value was decreased even in 4-week-old SHRSP.

Animals↗

PubMed1999

Treating neonatal rats with 6-hydroxydopamine induced an increase in voluntary alcohol consumption.

Brain dopamine (DA) and serotonin (5-HT) neurotransmission have been implicated in the mediation of alcohol-seeking behavior. We examined the effects of treatment of neonatal rats (3 days after birth) with the neurotoxin 6-hydroxydopamine (6-OHDA; 100 microg/10 microl, intracerebroventricularly) on the relationship between the levels of neurotransmitters and alcohol drinking behavior at the age of 14 weeks. 6-OHDA treatment reduced the levels of DA and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens (ACC), frontal cortex, striatum (STR), tegmentum/substantia nigra, and dorsal raphe nucleus. 5-HT levels in the ACC and STR were increased in the 6-OHDA-treated rats. 6-OHDA-treated rats showed increased alcohol consumption. There was a significant change in the ratio of [5-hydroxyindoleacetic acid]/[5-HT] in the ACC and STR of the treated rats, but no difference in the ratio of [DOPAC]/[DA] between the sham-operated controls and treated rats. 6-OHDA-treated rats had dopaminergic dysfunction in the five brain regions related to the reward system, in part, and a decrease in 5-HT turnover, including the accumulation of 5-HT in the ACC and STR. Furthermore, basal extracellular releases of DA and 5-HT of the ACC were significantly lower in the 6-OHDA-treated rats, compared with the controls. It was suggested that alcohol seeking behavior is associated with the alterations of dopaminergic neurons and the release of 5-HT in the mesocorticolimbic system.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1999

A typical bacterial ornithine-containing lipid Nalpha-(D)-[3-(hexadecanoyloxy)hexadecanoyl]-ornithine is a strong stimulant for macrophages and a useful adjuvant.

Nalpha-[3-(Hexadecanoyloxy)hexadecanoyl]-ornithine is a typical bacterial ornithine-containing lipid (OL). The configuration of the 3-hydroxy fatty acids in the OL was proved to be D by using HPLC with chiral column. For this analysis, Nalpha-(D or L)-[3-(hexadecanoyloxy)hexadecanoyl]-L-ornithine were synthesized and used as standards. The typical bacterial OL, as well as the synthesized one, exhibited strong interleukin-1- and prostaglandin E2-inducing activities, and further, it induced the production of high IgG anti-tetanus toxoid antibodies in mice. The typical OL is expected to be utilized as a nontoxic, potent adjuvant.

Adjuvants, Immunologic↗