Search PubMed⌕ Search

Biomedical subjects

Y Deguchi

Publications and source records attributed to Y Deguchi.

At least 91 records · Page 5Linked to original sources
PubMed1991

In vivo transport of a dynorphin-like analgesic peptide, E-2078, through the blood-brain barrier: an application of brain microdialysis.

In vivo transport through the blood-brain barrier (BBB) has been demonstrated for a dynorphin-like analgesic peptide, CH3-[125I]Tyr-Gly-Gly-Phe-Leu-Arg-CH3Arg-D-Leu-NHC2H5 ( [125I]E-2078). A remarkable time-dependent increase in the distribution volume of [125I]E-2078 in the brain parenchyma separated from blood vessels and capillaries was observed during a brain perfusion. The distribution volume of [125I]E-2078 in the brain parenchyma after 20 min of perfusion was 2.18 +/- 0.09 microliters/g brain (mean +/- SE) and was significantly greater than the distribution volume of [3H]inulin (0.994 +/- 0.138 microliters/g brain), providing in vivo evidence for the penetration of [125I]E-2078 into the brain parenchyma. Brain microdialysis was carried out to collect directly the brain interstitial fluid (ISF) during the brain perfusion of [125I]E-2078. No metabolite of [125I]E-2078 in the brain ISF was found by high-performance liquid chromatographic analysis of the brain dialysate. The concentrations of [125I]E-2078 and [14C]sucrose in the brain ISF were estimated based on an in vitro evaluation of dialysis clearance. The concentration ratio of [125I]E-2078 between the brain ISF and the brain perfusate was determined to be 2.92 x 10(-1) +/- 0.50 x 10(-1) and was approximately 100 times higher than that of [14C]sucrose (2.71 x 10(-3) +/- 1.43 x 10(-3), demonstrating transport of [125I]E-2078 through the BBB in vivo. On the other hand, no remarkable difference in the cerebrospinal fluid (CSF)-to-perfusate concentration ratios of [125I]E-2078 and [14C]sucrose was observed, indicating little contribution of the blood-CSF barrier (BCSF barrier) transport to the penetration of [125I]E-2078 into the brain.

Amino Acid Sequence↗
PubMed1991

Tumour necrosis factor/cachectin plays a key role in autoimmune pulmonary inflammation in lupus-prone mice.

The role of tumour necrosis factor-alpha (TNF-alpha) in the development of autoimmune pulmonary inflammation has been investigated in lupus-prone mice. An increase in TNF-alpha mRNA level from whole lung preparation of lupus-prone mice was evident, from 3 weeks to 12 weeks during growing process, as shown by Northern blot analysis, but not in control mice. Furthermore, it is also found that the major source of this increase in TNF-alpha mRNA was attributed to infiltrating mononuclear cells found within the lung. Treatment of lupus-prone mice with rabbit anti-mouse TNF-alpha IgG prevented the development of pulmonary inflammation lesions such as lung fibrosis and alveolitis. These results suggest that an increased TNF-alpha production by infiltrating mononuclear cells in the lungs of lupus-prone mice may play a role in the development of autoimmune pulmonary inflammation and in significant changes of cytokines and the immune responses in pulmonary inflammation lesions of lupus-prone mice.

Animals↗
PubMed1991

Spontaneous activation of transforming growth factor-beta gene transcription in broncho-alveolar mononuclear cells of individuals with systemic autoimmune diseases with lung involvement.

The spontaneous elevation of the transcription of the transforming growth factor-beta (TGF-beta) gene in broncho-alveolar mononuclear cells (BMC) of individuals with autoimmune diseases with lung involvement, by nuclear run-on transcription assay, is shown in this study. In quantification analysis of TGF-beta gene transcription, we found more than 10 times the enhanced transcription of the TGF-beta gene in BMC of individuals with autoimmune diseases with lung involvement, in comparison to normal healthy subjects or patients with bronchial asthma used as controls. Our observation suggests that TGF-beta, a potent mitogen for fibroblasts, may be produced in BMC during an active immune response in individuals with systemic autoimmune diseases with lung involvement, and may be involved in autoimmune-related pathophysiological changes of cytokine networks in lung involvement such as lung fibrosis.

Autoimmune Diseases↗
PubMed1991

Muscle microdialysis as a model study to relate the drug concentration in tissue interstitial fluid and dialysate.

The steady-state dialysis kinetics in buffer, erythrocyte suspension and muscle have been analyzed by clearance theory in the microdialysis study. "Tube" model has been demonstrated to be a useful model to relate the dialysis clearance, CLD, the dialysis flow rate, F, and the permeability rate constant, PA, for microdialysis employing the transcranial type microdialysis probe. The effective dialysis coefficient (Rd), defined as the ratio of the in vivo PA and in vitro PA, was introduced to account for the differences between in vivo and in vitro microdialyses. The Arrhenius plot of the antipyrine permeability rate constant presented a single straight line in the range of 15-37 degrees C with an activation energy of 5.49 kcal/mol. A fairly good correlation was observed between the reciprocal of the permeability rate constant and the root of the molecular weight in the range of 18-1039. On the contrary, the molecular weight and the plasma membrane permeability were not determinant factors for Rd value determined in the erythrocyte suspension (Rd,erythrocyte), while the interstitial fluid space (100-hematocrit)% of erythrocyte suspension plays a dominant factor to change Rd,erythrocyte. The in vivo permeability rate constant was determined in the muscle for [3H]water, [14C]urea, antipyrine and [14C]sucrose under the steady-state condition. No significant difference of Rd in muscle tissue was demonstrated for these four model substances. By using the Rd value, a hypothetical equation has been proposed to relate the concentration in the dialysate and the interstitial fluid at steady-state.

Animals↗
PubMed1991

Relationship between serum selenium concentration and atherogenic index in Japanese adults.

In mass health screening of the inhabitants of a coastal district in Fukui Prefecture, venous blood samples were collected from 304 men (aged 22-87 years) and 223 women (aged 23-84 years). We examined whether serum selenium concentration was related to atherogenic index [= (total serum cholesterol--high-density-lipoprotein cholesterol)/high-density-lipoprotein cholesterol] by multiple regression analysis with age, body mass index, and smoking and drinking habits as independent variables. Atherogenic index was a significant increasing factor of serum selenium concentration in the entire male subjects and the female subjects aged above 60 years.

Adult↗
PubMed1991

Sex differences in excretion of zenarestat in rat.

1. Rat shows a marked sex difference in the excretion of 14C-zenarestat: only 1% of the dose was excreted in the urine of males, about 45% of the dose was excreted in the urine of females. 14C in the urine of female rats was almost entirely unchanged drug. 2. Plasma protein binding was similar in both sexes: 99.3-99.5% in males and 99.4-99.6% in females. 3. The type and ratio of metabolites in the faeces and bile were not significantly different between males and females. 4. Renal clearance experiments, and inhibition of urinary excretion by probenecid, indicated that female rats may possess an active secretory mechanism which is lacking or relatively inactive in male rats.

Aldehyde Reductase↗
PubMed1991

Enhanced expression of heat shock protein gene in kidney lymphoid cells of lupus-prone mice during growing process.

In the present study, the spontaneous elevation of the transcription of heat shock protein (hsp 70) gene in kidney lymphoid cells of lupus-prone mice (MRL-lpr/lpr) is shown by Northern blot and nuclear run on transcription assay. By quantification analysis of hsp 70 gene transcription, more than ten times of the enhanced transcription of hsp 70 gene in kidney lymphoid cells of lupus-prone mice was first found, in comparison to normal control mice (MRL(-)+/+). The elevation of transcriptional level of hsp 70 gene was also found to increase during growing process and seemed to have positive correlation with deterioration of lupus-related renal disorders in lupus-prone mice. Our observation suggests that heat shock proteins may be involved in possible significance in the pathophysiology of nephrotic lesions of lupus-prone mice due to lupus-related change of kidney lymphoid cells.

Animals↗
PubMed1991

Cloning of a human homeobox gene that resembles a diverged Drosophila homeobox gene and is expressed in activated lymphocytes.

A new homeobox gene, HB24, has been isolated from a human B-lymphocyte cDNA library. Northern blot analysis of polyadenylated RNA purified from activated human B cells revealed a single mRNA transcript of approximately 2.3 kb. Two cDNA clones were sequenced and provided 2,250 nucleotides (nt) of DNA sequence information. There is a single methionine codon-initiated open reading frame of 1,458 nt in frame with a homeobox and a CAX repeat, and the open reading frame is predicted to encode a protein of 51,659 daltons. When the homeodomain from HB24 was compared to known mammalian and Drosophila homeodomains it was found to be only moderately conserved, but when it was compared to a highly diverged Drosophila homeodomain, H2.0, it was found to be 80% identical. The HB24 mRNA was absent or present at low levels in normal B and T lymphocytes; however, with the appropriate activation signal HB24 mRNA was induced within several hours even in the presence of cycloheximide. Characterization of HB24 expression in lymphoid and select developing tissues was performed by in situ hybridization. Positive hybridization was found in thymus, tonsil, bone marrow, developing vessels, and in fetal brain. HB24 is likely to have an important role in lymphocytes as well as in certain developing tissues.

Amino Acid Sequence↗
PubMed1991

Effects of the anticholinergic drug prifinium bromide on urinary bladder contractions in rat in vivo and in guinea-pig in vitro.

The parenteral and enteral effects of prifinium bromide (CAS 4630-95-9; in the following referred to as prifinium), a quaternary ammonium anticholinergic drug, were investigated on contractions of the rat urinary bladder by cystometry and compared with those of atropine, oxybutynin and terodiline. Additionally, in vitro experiments were carried out with the isolated guinea-pig detrusor muscle to clarify the mechanisms of action of these effects. In intravenous doses, all the drugs reduced the amplitude of the contractions in the cystometric studies. The inhibition was dose-dependent, but was not entirely even at the respective largest doses. According to the 40% inhibitory doses, prifinium was as active as atropine, and 10 and 100 times more active than oxybutynin and terodiline, respectively. The potency ratios of the drugs in their in vivo effects were in good agreement with those of their in vitro anticholinergic effects, which were determined with carbachol-induced contractions in the isolated guinea-pig detrusor muscle. On the other hand, in the in vitro studies, prifinium and atropine had little or no effect on contractions induced by electrical stimulation, KCl and BaCl2, whereas oxybutynin and terodiline antagonized all of the stimuli to a similar extent. These findings indicate that the anticholinergic activity of prifinium may be only one factor in the mechanisms of its in vivo inhibition of the rat bladder contractions. Finally, intraduodenal doses of prifinium also inhibited the contractions of the rat bladder, and the effects of the drug by this route were almost the same as those of oxybutynin and terodiline.

Animals↗
PubMed1990

Nucleotide sequence of gltS, the Na+/glutamate symport carrier gene of Escherichia coli B.

The nucleotide sequence of the gltS gene coding for an Na+/glutamate symport carrier of Escherichia coli B has been determined, and the amino acid sequence of the carrier protein was deduced. The predicted glutamate carrier consists of 401 amino acids with a molecular weight of 42,455. A Shine-Dalgarno sequence and putative promoter sequences were found in the 5'-flanking region of the putative gltS gene. The predicted protein is very hydrophobic (73% nonpolar amino acids), and judging from its hydropathy profile, the protein is composed of 12 hydrophobic membrane-spanning segments with a mean length of 21.6 residues/segment. A typical rho-independent transcription termination signal was found downstream of the gltS gene. We found a conserved alignment of 5 amino acid residues (Gly42--Ala82-X-X-X-X-Leu87-X-X-X-Gly91-Arg92 ), which commonly exists in four Na+ symport carrier proteins, the glutamate carrier, and the proline carrier of E. coli, and the Na+/glucose co-transporters of rabbit and human intestines. We propose that this consensus sequence (or motif) may play an important role in cation recognition or binding in the Na+/solute symport reaction.

Amino Acid Sequence↗
PubMed1990

The effect of taurine on age-related immune decline in mice: the effect of taurine on T cell and B cell proliferative response under costimulation with ionomycin and phorbol myristate acetate.

Proliferative responses to the costimulation with phorbol-12-myristate-13-acetate (PMA) and suboptimal doses of ionomycin in the purified T and B cells from old mice were lower than those from young mice. The degree of the age-related decline was more significant in T cells than in B cells. Taurine, a sulfur containing amino acid, augmented the proliferative responses of T cells from both young and old mice. The augmentation of the proliferative response by taurine was more marked in old T cells than in young ones. The concentration of intracellular free calcium ion ([Ca2+]i) was significantly lower in the old T cells under the stimulation with PMA and ionomycin than that in the young ones. In the presence of taurine, the concentration of [Ca2+]i in the old T cell significantly increased under the stimulation. The results indicate that taurine improved the proliferative response of old T cells by the restoration of the increment of the concentration of [Ca2+]i under the stimulation.

Aging↗
PubMed1990

Spontaneous activation of heat shock protein gene transcription in peripheral blood mononuclear cells of individuals with active systemic lupus erythematosus.

In the present study, we show the spontaneous elevation of the transcription of heat shock protein (hsp 70) gene in peripheral blood mononuclear cells (PBMC) of individuals with active systemic lupus erythematosus (SLE) by nuclear run-on transcription assay. For quantification analysis of hsp 70 gene transcription, we first found more than ten times of the enhanced transcription of hsp 70 gene in PBMC of individuals with active SLE, as compared to normal healthy subjects or patients with bronchial asthma as controls. Our observation suggests that heat shock proteins may be produced during an active immune response in individuals with active systemic lupus erythematosus and is involved in lupus-related change of possible essential function in PBMC.

Female↗
PubMed1990

Interleukin 6 and expression of its receptor on epidermal keratinocytes.

Interleukin 6 (IL 6) was detected in the culture supernatants of human epidermal keratinocytes and its production was enhanced by stimulation with cytokines. Production of IL 6 in keratinocytes was demonstrated directly by immunohistochemical staining of cultured cells with anti-IL 6 antibody. Keratinocyte-growth was increased by stimulation with recombinant IL 6 (as measured by either [3H] thymidine uptake or direct cell count). Moreover, expression of IL 6 receptor was demonstrated on monolayered cells, and the deeper cells of stratified keratinocytes in culture by immunohistochemistry. On the other hand, differentiated cells in the upper layers did not express IL 6 receptor on their surfaces, suggesting that the expression of IL 6 receptors may be confined to the proliferative cells. Thus, IL 6, which is produced by epidermal keratinocytes, may be involved in the regulation of normal keratinocyte growth.

Cell Division↗
PubMed1990

Elevated expression of heat-shock protein gene in the fibroblasts of patients with scleroderma.

1. Scleroderma is a systemic autoimmune disorder characterized by fibrosis affecting the skin, lung, kidney and other organs. The 70 kDa heat-shock protein has been implicated as essential for cell function during cell growth and differentiation. To study the molecular basis of intracellular events in sclerotic fibroblasts, we compared the expression of the hsp 70 gene in sclerotic and normal control fibroblasts by a run on nuclear transcription assay and a Northern blot assay. 2. In the run on nuclear transcription assay, sclerotic fibroblasts expressed an approximately eightfold higher level of hsp 70 transcription than normal fibroblasts in the quiescent condition after serum starvation. After stimulation with serum, the transcription level of the hsp 70 gene was almost similar in sclerotic and normal control fibroblasts. 3. In the Northern blot assay, the hsp 70 gene transcript, which was present in increased amounts in sclerotic fibroblasts, exhibited normal size.

Blotting, Northern↗
PubMed1990

Tumor necrosis factor changes sensitivity of differentiation of mouse leukemia M1 cells by lipopolysaccharide.

A clone of mouse leukemia M1 cells was induced to differentiate by lipopolysaccharide (LPS) (LPS-sensitive clone) while another clone of the same cells was resistant (LPS-resistant clone). LPS and lipid A preparations from Pseudomonas diminuta and Pseudomonas vesicularis were as active as Escherichia coli LPS in the induction of differentiation of the LPS-sensitive clone. Synthetic lipid A precursor Ia (compound 406), which has no interleukin 1 (IL-1)-inducing activity toward monocytes, had strong differentiation-inducing activity toward the LPS-sensitive clone. The combined treatment of the LPS-sensitive clone with LPS and recombinant tumor necrosis factor (rTNF) did not further increase the degree of differentiation induced by LPS alone. By contrast, the LPS-resistant clone was markedly induced to differentiate by LPS in the presence of rTNF. Combined treatment of the LPS-resistant clone with LPS and other cytokines such as recombinant IL-1 alpha, recombinant granulocyte colony-stimulating factor, and interferon-gamma was not effective in inducing marked synergistic differentiation. These results raise the possibility that rTNF changes the sensitivity of M1 cells to induction of differentiation by LPS.

Animals↗
PubMed1990

Enhanced expression of the tumour necrosis factor/cachectin gene in peripheral blood mononuclear cells from patients with systemic vasculitis.

The expression of tumour necrosis factor-alpha (TNF-alpha) gene in peripheral blood mononuclear cells from patients with systemic vasculitis, periarteritis nodosa and Wegener's granulomatosis, has been studied by RNA dot blot and Northern blot assays. We further examined the transcriptional level of TNF-alpha gene in peripheral blood mononuclear cells from these patients by performing nuclear run on transcription assay. We demonstrate enhanced TNF-alpha gene expression in mononuclear cells from these patients compared with healthy subjects and patients with bronchial asthma. These findings suggest that the enhanced transcription of TNF-alpha gene in peripheral blood mononuclear cells from patients with systemic vasculitis may be involved in the pathophysiology/pathogenesis of these diseases by cytokine dysregulation.

Adult↗
PubMed1990

Elevated transcription of heat shock protein gene in scleroderma fibroblasts.

Scleroderma is a systemic disorder characterized by fibrosis, which affects skin, lung, kidney and other organs. Heat shock protein (hsp) (70 kD) has been implicated as an essential element of cell function in cell growth and differentiation. To study the molecular basis of intracellular events in scleroderma fibroblasts, we compared the expression of hsp 70 gene in scleroderma and normal control fibroblasts by nuclear run on transcription assay and Northern blot assay. We show that scleroderma fibroblasts express more than eight times higher level of hsp 70 transcription in normal control fibroblasts at quiescent conditions in the absence of serum. After stimulation with serum, the transcription level of the hsp 70 gene is similar in scleroderma and normal control fibroblasts. Therefore, our results indicate an alteration/activation of intracellular events in scleroderma fibroblasts.

Adult↗