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Biomedical subjects

T Hada

Publications and source records attributed to T Hada.

At least 55 records · Page 3Linked to original sources
PubMed1999

Kupffer cells from Schistosoma mansoni-infected mice participate in the prompt type 2 differentiation of hepatic T cells in response to worm antigens.

Infection with Schistosoma mansoni, a portal vein-residing helminth, is well known to generate life cycle-dependent, systemic immune responses in the host, type 1 deviation during the prepatent period, and type 2 polarization after oviposition. Here we investigated local immunological changes in the liver after infection. Unlike splenocytes, hepatic lymphocytes from infected mice during the prepatent period already produced a higher amount of IL-4 and a lesser amount of IFN-gamma than those from uninfected mice. Hepatic lymphocytes, particularly conventional T cells, but not NK1.1+ T cells, promptly produced IL-4 in response to worm products, soluble worm Ag preparation (SWAP), whenever presented by Kupffer cells from infected mice. The hepatic lymphocytes that had been stimulated with SWAP presented by infected mice-derived Kupffer cells produced a huge amount of IL-4, IL-13, and IL-5 as well as little IFN-gamma in response to immobilized anti-CD3 mAb. Kupffer cells from uninfected mice produced IL-6 and IL-10, but not IL-12 or IL-18, in response to SWAP stimulation and gained the potential to additionally produce IL-4 and IL-13 after the infection. These results suggested that prompt type 2 deviation in the liver after the infection might be due to the alteration of Kupffer cells that induces SWAP-mediated type 2-development of hepatic T cells.

Animals↗
PubMed1999

IL-18 up-regulates perforin-mediated NK activity without increasing perforin messenger RNA expression by binding to constitutively expressed IL-18 receptor.

IL-18 is a powerful inducer of IFN-gamma production, particularly in collaboration with IL-12. IL-18, like IL-12, also augments NK activity. Here we investigated the molecular mechanism underlying the up-regulation of killing activity of NK cells by IL-18. IL-18, like IL-12, dose dependently enhanced NK activity of splenocytes. This action was further enhanced by costimulation with IL-12. Treatment with anti-IL-2R Ab did not affect IL-18- and/or IL-12-augmented NK activity, and splenocytes from IFN-gamma-deficient mice showed enhanced NK activity following stimulation with IL-12 and/or IL-18. Splenocytes from the mice deficient in both IL-12 and IL-18 normally responded to IL-18 and/or IL-12 with facilitated NK activity, suggesting that functional NK cells develop in the absence of IL-12 and IL-18. IL-18R, as well as IL-12R mRNA, was constitutively expressed in splenocytes from SCID mice, which lack T cells and B cells but have intact NK cells, and in those from IL-12 and IL-18 double knockout mice. NK cells isolated from SCID splenocytes expressed IL-18R on their surface. IL-18, in contrast to IL-12, did not enhance mRNA expression of perforin, a key molecule for exocytosis-mediated cytotoxicity. However, pretreatment with concanamycin A completely inhibited this IL-18- and/or IL-12-augmented NK activity. Furthermore, IL-18, like IL-12, failed to enhance NK activity of splenocytes from perforin-deficient mice. These data suggested that NK cells develop and express IL-12R and IL-18R in the absence of IL-12 or IL-18, and that both IL-18 and IL-12 directly and independently augment perforin-mediated cytotoxic activity of NK cells.

Animals↗
PubMed1999

Stimulation of hyaluronan synthesis by tumor necrosis factor-alpha is mediated by the p50/p65 NF-kappa B complex in MRC-5 myofibroblasts.

The lesions of fibrocontractive diseases result from an excessive myofibroproliferative response to numerous forms of inflammatory stimuli, which elicit the net deposition of extracellular matrix (ECM) in the interstitium of the affected tissue. Hyaluronan (HA), reported to be a key player supporting cellular migration and adherence, is a major component of ECM that undergoes dynamic regulation during inflammation. The molecular regulation of HA biosynthesis by inflammatory cytokines on myofibroblasts is not yet completely understood. Here we report the biochemical characteristics of the lung myofibroblast cell line MRC-5, and we demonstrate that the production of HA by this cell line is inducible by the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), at the message level of HA synthase (HAS). In TNF-alpha-stimulated MRC-5 cells, DNA-binding and competition experiments indicated that the predominant NF-kappa B binding activity detected with nuclear extract-stimulated cells is mediated by the p50/p65 complex. Using antisense oligonucleotides, we confirmed that the TNF-alpha-stimulation of HA synthesis by MRC-5 cells is dependent on the activation of the p50/p65 NF-kappa B complex. These findings indicate that TNF-alpha production within inflamed tissues may enhance the HA synthesis via the transcriptional induction of HAS on myofibroblasts, thereby providing a provisional matrix for supporting cellular migration and adhesion, and that the p50/p65 NF-kappa B complex that plays an important role in the regulation of HA production by TNF-alpha might be an appropriate target for therapeutic compounds to treat tissue fibrosis accompanied by inflammation.

Actins↗
PubMed1999

Discrimination of liver cirrhosis from chronic hepatitis by measuring the ratio of Aleuria aurantia lectin-reactive serum cholinesterase to immunoreactive protein.

We have previously reported that Aleuria aurantia lectin (AAL)-reactive serum cholinesterase (ChE) activity increases in liver cirrhosis (LC) and hepatocellular carcinoma (HCC) compared with chronic hepatitis (CH) and normal controls (NC), and measurement of AAL-reactive ChE activity is useful in discriminating LC from CH. In the present study, we have demonstrated that the measurement of the ratio of AAL-reactive ChE to immuno-reactive ChE protein (AAL/ChE) is superior to the measurement of only AAL-reactive ChE for differentiating LC from CH. At a cut-off value of 4.0 arbitrary units of AAL/ChE, the diagnostic accuracy was 87.7%. This diagnostic accuracy is similar to that of serum hyaluronan, 88.8%. We also examined whether the AAL/ChE measurement is useful for differentiating Child's stage A LC from chronic active hepatitis (CAH) 2B. When mean + 2SD of AAL/ChE in patients with CAH2B was used as a cut-off value for the specific diagnosis of LC, the diagnostic accuracy was 70.2%. These results demonstrate that measurement of AAL/ChE is useful for discriminating LC from CH.

Cholinesterases↗
PubMed1999

Plasma levels of pipecolic acid, both L- and D-enantiomers, in patients with chronic liver diseases, especially hepatic encephalopathy.

Pipecolic acid is regarded as a gamma-aminobutyric acid receptor agonist. Stereochemical studies of pipecolic acid were performed in patients with chronic liver diseases. Plasma D- and L-pipecolic acid were significantly elevated in 15 liver cirrhotic patients with no history of hepatic encephalopathy (1.05+/-0.24 micromol/l, 1.58+/-0.13 micromol/l, p < 0.01) and in 27 patients with chronic hepatic encephalopathy (1.58+/-0.50 micromol/l, 2.38+/-0.58 micromol/l, p<0.001) compared to 15 normal subjects. In seven patients with chronic hepatic encephalopathy orally treated with kanamycin, plasma pipecolic acid significantly decreased (D-acid: before 1.62+/-0.23 micromol/l, after 0.61+/-0.15 micromol/l; p<0.01, L-acid: before 2.43-0.52 micromol/l, after 2.23+/-0.11 micromol/l; p< 0.05). These results suggest that plasma pipecolic acid, particularly D-acid, is produced from D-lysine by intestinal bacteria in liver cirrhotic patients and that pipecolic acid could be involved in the pathogenesis of hepatic encephalopathy.

Adult↗
PubMed1999

Origin of D- and L-pipecolic acid in human physiological fluids: a study of the catabolic mechanism to pipecolic acid using the lysine loading test.

Pipecolic acid, a metabolite of lysine, is found in human physiological fluids. It is known that plasma pipecolic acid levels are elevated in patients with Zellweger syndrome, a genetic disorder, and chronic liver diseases. However, it is uncertain if this acid originates directly from food intake or from mammalian or intestinal bacterial enzyme metabolism. To characterize the relationship between plasma pipecolic acid and diet, we analyzed the contents of pipecolic acid in 17 edible plants and changes in plasma and urinary pipecolic acid levels following soybean juice ingestion by 4 healthy volunteers. Our study revealed that some of the plants contained high concentrations of total pipecolic acid, and a higher portion of L-isomer than D-isomer. Loading tests demonstrated that plasma levels and urinary excretion of D-isomer increased significantly 2 h after soybean juice ingestion. Plasma lysine levels showed a similar increase to that of D-isomer. These findings suggest that plasma pipecolic acid, particularly the D-isomer, originates mainly from the catabolism of dietary lysine by intestinal bacteria rather than by direct food intake and that D- and L-isomer may have different mechanisms of metabolism. Moreover, these findings may be important for clarifying the pathogenesis of peroxisomal disorders.

Chromatography, High Pressure Liquid↗
PubMed1999

Caspase-1-independent, Fas/Fas ligand-mediated IL-18 secretion from macrophages causes acute liver injury in mice.

IL-18, produced as a biologically inactive precursor, is processed by caspase-1 in LPS-activated macrophages. Here, we investigated caspase-1-independent processing of IL-18 in Fas ligand (FasL)-stimulated macrophages and its involvement in liver injury. Administration of Propionibacterium acnes (P. acnes) upregulated functional Fas expression on macrophages in an IFNgamma-dependent manner, and these macrophages became competent to secrete mature IL-18 upon stimulation with FasL. This was also the case for caspase-1-deficient mice. Administration of recombinant soluble FasL (rFasL) after P. acnes priming induced comparable elevation of serum IL-18 in parallel with elevated serum liver enzyme levels. However, liver injury was not induced in IL-18-deficient mice after rFasL administration. These results indicate a caspase-1-independent pathway of IL-18 secretion from FasL-stimulated macrophages and its critical involvement in FasL-induced liver injury.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Is ventilation during maximal exercise limited by dynamic airway closure?

A study was undertaken to find if the reason why horses hypoventilate when running is that they experience expiratory flow limitation due to dynamic airway closure. To test this hypothesis, we measured peak expiratory flows on a Thoroughbred galloping on a treadmill and hypoventilating and compared those flows with the peak dynamically-limited flow that the same horse could achieve during a forced expiratory flow-volume manoeuvre. At the approximate lung volumes at which the horse was ventilating while running, it did not appear to be mechanically limited and appeared to have reserve capacity available potentially to increase its expiratory flow.

Animals↗
PubMed1999

Changes in left ventricular dynamics during graded exercise.

Three mature Thoroughbred horses were prepared surgically with ultrasonic sonomicrometer crystals affixed to their ventricular pericardia. Signals from crystals recorded dimensions of axes across the left ventricle. Cubic algorithms were fitted to dimensional data to generate volume estimates that matched stroke volumes simultaneously measured using the Fick principle. As horses stood at rest or exercised at various intensities (approx 7, 12, 24, 47 and 100% maximal rate of O2 consumption VO2max[), left ventricular dimensions were recorded and 20 consecutive diastolic and systolic volumes calculated. Although Fick estimates detected no difference in stroke volume at different exercise intensities, sonomicrometer measurements of stroke volume were significantly lower at rest and higher at VO2max. These differences mirrored changes in end-diastolic volume, although end-systolic volume did not change. At all exercise intensities, stroke volume was most variable and end-diastolic volume the least. The pattern conforms to the Frank-Starling mechanism, and indicates that at high exercise intensities ventricular myocytes generate high pressures with higher myocardial wall stress due to the increased size of the chamber.

Animals↗
PubMed1999

Cardiac output measurements using sonomicrometer crystals on the left ventricle at rest and exercise.

Eight horses were fitted surgically with 8 ultrasonic sonomicrometer crystals each attached to their left ventricular pericardia and a left atrial catheter. Three horses returned to treadmill performance with a maximum rate of oxygen consumption similar to their presurgical values. These horses were evaluated to determine how well sonomicrometer estimates of cardiac output agreed with those obtained by a steady-state method, the Fick principle. Variance between the 2 was similar to the coefficient of variation (approximately 12.5%) of the Fick estimates. We conclude that left ventricular sonomicrometer measurements in horses appear to give a reasonable estimate of ventricular dimensions and can, therefore, be used potentially to evaluate such variables as diastolic flow.

Animals↗
PubMed1999

[Successful treatment for disseminated intra-vascular coagulation due to sepsis and brain abscess with low molecular weight heparin in a patient with antiphospholipid syndrome].

The management of disseminated intravascular coagulation (DIC) in a 22-year-old female patient with antiphospholipid syndrome is reported. Gabexate mesilate was given by continuous drip infusion at 1.5 g/day. No effect was seen, therefore Dalteparin sodium (DS) was administered by continuous drip infusion at 70 U/kg/day. The DIC score improved gradually during the first 4 days to normalization by 10 days. However, convulsive seizure was developed. Computed tomographic scan of brain demonstrated brain abscess at lt-basal ganglia. Continuous drainage was performed while administered continuous drip infusion of DS. Follow-up CT after operation showed reduction of low density area which means brain abscess. Finding in this case suggest that DS may play a role in the management of DIC accompanying intracranial infection.

Adult↗
PubMed1999

[Usefulness of combination therapy with expandable metallic stent replacement and FLEP chemotherapy (consisting of 5-FU, leucovorin, etoposide and cisplatin) for advanced esophageal cancer invading the bronchus: a case report].

A 63-year-old male with an esophageal cancer invading the bronchus was treated with radiation therapy (70 Gy) from November 1995, resulting in the disappearance of the lesion. He was later readmitted due to dysphagia from the recurrence of the esophageal cancer. We diagnosed, by endoscopic and chest CT scan findings, that the esophageal cancer was invading the right bronchus. We inserted an expandable metallic stent endoscopically, and the patient could eat well. We performed two courses of FLEP chemotherapy (consisting of 5-FU, leucovorin, etoposide and cisplatin) from November 12, 1997. He then suffered from an esophagobronchial fistula, but was cured by a covered expandable metallic stent replacement. No esophageal stenoses or recurrences were seen endoscopically and he could eat well on December 7, 1998. The standard modality of treatment for patients with advanced esophageal cancer invading adjacent structures is not yet established, and the prognosis for such patients remains quite poor. We performed combination therapy with an expandable metallic stent replacement and FLEP chemotherapy, and improved the patient's quality of life. This form of therapy was thus proved useful for patients with esophageal cancer invading adjacent structures.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Induction of calponin-h1 by transforming growth factor-beta1 in cultured human ito cells, LI90.

We investigated the effect of transforming growth factor-beta1 (TGF-beta1) on the expression of calponin-h1, alpha-smooth muscle actin (alpha-SMA), and extracellular matrix (ECM) components in a cultured human Ito cell line, LI90. The TGF-beta1 treatment stimulated productions of hyaluronic acid and laminin, and significantly decreased the secretion of hepatocyte growth factor in LI90 cells. The functional characteristics of LI90 cells were compatible with those of human-activated Ito cells that are known as pericyte-like mesenchymal liver cells. TGF-beta1 induced a slight growth-inhibition of LI90 cells. TGF-beta1 enhanced the expressions of both alpha-SMA and calponin-h1 at the protein level, while tumor necrosis factor-alpha and interleukin-1alpha did not affect the expressions of these cytoskeletal proteins on LI90 cells. The addition of TGF-beta1 to LI90 cells resulted in a significant increase of calponin-h1 mRNA levels, but not calponin-h2. These data suggest that the expression of calponin-h1 is controlled at the level of mRNA under the coordinate regulation together with alpha-SMA as the process of perpetuation of activated Ito cells promoted by TGF-beta1. The identification of smooth muscle features promoted by TGF-beta1 support the hypothesis that the activation of Ito cells coincides with their contractile behavior, indicating that these cells may be important in vasoregulation during liver injury and fibrosis.

Actins↗
PubMed1998

A novel method for determination of alpha1,6fucosyltransferase activity using a reducing oligosaccharide from egg yolk as a specific acceptor.

A new method for determination of alpha1,6fucosyltransferase activity has been described. Recently, the disialyl-biantennary undecasaccharide was prepared in high yield from egg yolk [(1996), Carbohydr Lett 2: 137-42]. By treatment of this oligosaccharide with neuraminidase and beta-galactosidase, we readily obtained an asialo-agalacto-biantennary heptasaccharide (GlcNAcbeta 1,2Manalpha1,6[GlcNAcbeta1,2Manalpha1,3]Manbeta1 ,4GlcNAcbeta1,4GlcNAc). Using this asialo-agalacto-oligosaccharide as an acceptor, fucosyltransferases from human plasma and extracts of various human hepatoma cell lines were assayed in the presence of GDP-[3H]fucose. The reaction mixture was applied to a column of GlcNAc-binding, Psathyrella velutina lectin coupled gel. All the fucosylated acceptor were bound to the column which was eluted with 50 mM GlcNAc. Structural analyses revealed that only the innermost GlcNAc residue of the acceptor was fucosylated through an alpha1,6-linkage, and the oligosaccharide prepared could be used as a specific acceptor for alpha1,6fucosyltransferase. The present method was used to screen plasma alpha1,6fucosyltransferase in several patient groups, and significantly elevated activities were found in samples from patients with liver diseases, including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.

Acetylglucosamine↗
PubMed1998

Elevated serum levels of Trichosanthes japonica agglutinin-I binding alkaline phosphatase in relation to high-risk groups for hepatocellular carcinomas.

The N-linked sugar chain structures of human hepatic, intestinal, and placental alkaline phosphatases (ALPs) were studied comparatively by chromatography on various lectin columns in combination with digestion by several kinds of exoglycosidases. The sugar chain structures were organ specific. On the basis of these organ-specific structures, we investigated serum ALP using a Neu5Ac(alpha)2-->6Gal(beta)1-->4 GlcNAc-specific Trichosanthes japonica agglutinin-I (TJA-I)-Sepharose column to clarify whether the level of TJA-I-binding serum ALP activity can be used as an indicator to discriminate one form of chronic liver disease from another. Levels of TJA-I-binding ALP in serum were higher in cases of liver cirrhosis and hepatocellular carcinoma than in chronic hepatitis (P < 0.01). The levels of TJA-I-binding ALP in serum did not change significantly after transcatheter arterial embolization, and the amounts of TJA-I-binding ALP activity in noncancerous cirrhotic liver tissues were higher than those in cancerous liver tissues derived from hepatocellular carcinoma patients, indicating that the TJA-I-binding ALP is mainly derived from cirrhotic liver tissues rather than cancerous liver tissues. These results indicate that analysis of the levels of TJA-I-binding ALP in serum is clinically useful for differentiating liver cirrhosis from chronic hepatitis and that altered sugar chain expression in ALP occurs mainly in liver cirrhosis.

Alkaline Phosphatase↗