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Biomedical subjects

K Yoshioka

Publications and source records attributed to K Yoshioka.

At least 343 records · Page 19Linked to original sources

Apolipoproteins and lipoprotein receptors in glomeruli in human kidney diseases.

This study offers morphological evidence of the involvement of lipid abnormalities in human glomerular injury. Renal biopsy tissues from patients with several types of glomerular diseases were immunocytochemically examined using antibodies to apolipoproteins (apo) A-I, B-100, and E, and antibodies to low density lipoprotein (LDL) receptors and scavenger receptors. Immunofluorescent staining showed the predominant deposition of apo B and apo E in the mesangial area in mesangial proliferative types of glomerulonephritis; the distribution and staining intensity of these apolipoproteins correlated with the grade of mesangial proliferation and proteinuria, but were independent of plasma lipid levels. Immunoelectron microscopy revealed that apo B and apo E were distributed in droplets within glomerular epithelial and mesangial cells or in a granular pattern in the expanded mesangial matrix. Apo A-I was mainly localized in the visceral epithelial cells of normal human kidneys. Staining for apo A-I was increased in the glomerular epithelial cells of nephritic kidneys, compared to the pattern in normal human kidneys, and was decreased in the sclerosed areas of glomeruli. An immunogold technique revealed the expression of LDL receptors on the surface membranes of glomerular mesangial and epithelial cells. Dual immunofluorescent staining showed that apo B and LDL receptors were occasionally co-localized in nephritic glomeruli. Scavenger receptor was detected on the plasma membranes of mesangial and visceral epithelial cells. The glomerular expression of scavenger receptor was increased in glomeruli with marked mesangial proliferation. In addition, the expression of this receptor was intense in monocytes/macrophages occasionally infiltrating the glomeruli. Our present findings indicate that in human nephritic kidneys, glomerular epithelial and mesangial cells express both LDL receptors and scavenger receptors. The accumulation of apolipoproteins, whether receptor-mediated or mediated by other mechanisms, can occur independently of plasma lipid levels, and may be associated with mesangial expansion and proteinuria.

Apolipoproteins↗

In situ expression of cytokines in IgA nephritis.

We studied mRNA and protein expression of interleukins (IL) and tumor necrosis factor (TNF) in renal tissues biopsied from 40 patients with IgA nephritis. Immunofluorescent staining with antibodies to IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha, and TNF-beta was intense in the cytoplasm of cells in glomeruli, which were dual-stained with an anti-monocyte-macrophage antibody. In addition, moderate immunofluorescence for TNF-alpha, and weak staining for IL-1 alpha and IL-6 were occasionally found in resident glomerular cells. Immunoperoxidase-in situ hybridization dual-labeling revealed that IL-1 alpha, IL-6, and TNF-alpha mRNA signals were present in intraglomerular cells reactive with anti-monocyte-macrophage antibody, which further supported the immunofluorescent findings. Cells expressing IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha, and TNF-beta were also observed in the interstitium. Most of these cells were also labeled with the anti-monocyte-macrophage antibody. The number of IL-1 alpha, IL-6, and TNF-alpha-positive cells infiltrating the glomerulus significantly correlated with mesangial hypercellularity. IL-8 and TNF-alpha-positive intraglomerular cells were correlated with the magnitude of proteinuria. The population of interstitial cells positive for IL-1 alpha, IL-6, IL-8, and TNF-alpha was associated with the grade of tubulointerstitial changes and proteinuria. There was no correlation between local IL-1 alpha, IL-6, and TNF-alpha expression in glomeruli or interstitium and serum or urinary levels of the respective cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Muscarinic excitatory and inhibitory mechanisms involved in afferent fibre-evoked depolarization of motoneurones in the neonatal rat spinal cord.

1. The involvement of acetylcholine and muscarinic receptors in spinal synaptic responses evoked by electrical and noxious sensory stimuli was investigated in the neonatal rat spinal cord in vitro. 2. Potentials were recorded extracellularly from a ventral root (L3-L5) of the isolated spinal cord, spinal cord-cutaneous nerve, and spinal cord-skin preparations of 1- to 4-day-old rats. Spinal reflexes were elicited by electrical stimulation of the ipsilateral dorsal root or the cutaneous saphenous nerve, or by noxious skin stimulation. 3. Single shock stimulation of supramaximum intensity of a dorsal root induced a mono-synaptic reflex in the corresponding ventral root. Bath-application of the muscarinic agonists, muscarine (0.3-30 microM) and (+)-cis-dioxolane (0.1-100 microM), produced an inhibition of the mono-synaptic reflex and a depolarization of motoneurones. Other muscarinic agonists, arecoline (10 nM-10 microM) and oxotremorine (10 nM-1 microM), inhibited the mono-synaptic reflex with little or no depolarization of motoneurones. Repetitive stimulation of the saphenous nerve at C-fibre strength induced a slow depolarizing response lasting about 30 s of the L3 ventral root. This slow ventral root potential (VRP) was also inhibited by arecoline (10 nM-10 microM) and oxotremorine (10 nM-1 microM). 4. In the spinal cord-saphenous nerve-skin preparation, a slow VRP was evoked by application of capsaicin (0.5 microM), bradykinin (3 microM), or noxious heat (47 degrees C) to skin. This slow VRP was depressed by the muscarinic agonists, arecoline (3 microM) and oxotremorine (1 microM). 5. Of the (+)-cis-dioxolane-induced inhibition of mono-synaptic reflex and motoneurone depolarization, the M2 antagonists, AF-DX 116 (0.1-1 microM) and methoctramine (100-300 nM), preferentially blocked the former response, whereas the M3 antagonists, 4-DAMP (3-10 nM) and p-F-HHSiD (0.3-3 microM), preferentially blocked the latter response. AF-DX 116 (0.1-1 microM) and methoctramine (100-300 nM) also effectively antagonized the arecoline- and oxotremorine-induced inhibition of the slow VRP. The pA2 values of AF-DX 116 and methoctramine against the arecoline-induced inhibition of the mono-synaptic reflex were both 6.79, and that of 4-DAMP against the (+)-cis-dioxolane-induced motoneurone depolarization was 8.16. 6. In the spinal cord-cutaneous nerve preparation, the saphenous nerve-evoked slow VRP was augmented by the anticholinesterase, edrophonium (5 microM). AF-DX 116 (1 microM) and methoctramine (100 nM) also potentiated the slow VRP, whereas 4-DAMP (10 nM) depressed the response. 4-DAMP(5-10 nM) depressed the capsaicin-induced slow VRP in the spinal cord-skin preparation.7. Oxotremorine (0.3 microM) and arecoline (1 AM) markedly depressed the depolarization of motoneurones evoked by application of capsaicin (3 9AM) to the spinal cord, whereas they depressed only slightly the depolarization induced by substance P (10 nM).8. The present study suggests that both excitatory (via M3-type receptors) and inhibitory (via M2-type receptors) muscarinic mechanisms are involved in afferent fibre-evoked nociceptive transmissions in the neonatal rat spinal cord.

Animals↗

Depression of primary afferent-evoked responses by GR71251 in the isolated spinal cord of the neonatal rat.

1. The pharmacological profile of GR71251, a new tachykinin receptor antagonist, and its effect on the responses evoked by stimulation of primary afferent fibres were studied in isolated spinal cord preparations of neonatal rats. Potential changes were recorded extracellularly from a lumbar ventral root (L3-L5). 2. Bath-application of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) at 0.01-3 microM to the spinal cord induced depolarization of the ventral root in normal artificial cerebrospinal fluid (CSF). The NK1 agonist, acetyl-Arg6-septide, and the NK3 agonist, senktide, at 0.01-3 microM, also had potent depolarizing actions whereas two NK2 agonists, beta-Ala8NKA4-10 and Nle10NKA4-10, showed little depolarizing effects at 1 microM. 3. GR71251 (0.3-3 microM) caused a rightward shift of the concentration-response curves for SP, acetyl-Arg6-septide and NKA with pA2 values of 6.14, 6.75 or 6.70, respectively. The effects of GR71251 were readily reversible within 15-30 min after its removal. By contrast, GR71251 (1-5 microM) had little effect on the depolarizing responses to NKB and senktide. 4. GR71251 (1-3 microM) did not depress the depolarizing responses to bombesin, neuromedin B and gastrin-releasing peptide in normal artificial CSF. 5. Application of capsaicin to the spinal cord induced a depolarizing response, which was partially depressed by GR71251 (3-10 microM). 6. In the isolated spinal cord preparation, intense electrical stimulation of a dorsal root evoked a slow depolarizing response of the contralateral ventral root of the same segment. A similar slow ventral root depolarization was evoked by electrical stimulation of the ipsilateral saphenous nerve in an isolated spinal cord-saphenous nerve preparation. GR71251 (0.3-10 microM) dose-dependently depressed these slow ventral root potentials.7. In the spinal cord-peripheral nerve preparation, conditioning stimulation of the saphenous nerve evoked an inhibition of the muscle nerve-evoked monosynaptic reflex lasting about 20 s. The late part of the inhibition was markedly depressed by GR71251 (1-3 microM).8. The present results indicate that GR71251 is a potent and specific antagonist for tachykinin receptors in the spinal cord. The present study further provides evidence for the involvement of SP and NKA in the slow ventral root depolarization and the prolonged inhibition of monosynaptic reflex that are evoked by primary afferent stimulation.

Analgesics↗

Contact allergies to topical corticosteroids.

The patient, a 34-year-old Japanese woman who noticed worsening of her rash after using topical corticosteroid preparations on her neck, was patch tested for both commercial preparations and corticosteroids themselves. The patch test results revealed that she had a contact allergy to gold, oxytetracycline, and 2 types of corticosteroid (acetonides and esters) in 7 compounds (betamethasone valerate and dipropionate, hydrocortisone butyrate and hydrocortisone butyrate propionate, amcinonide, budesonide, and fluocinonide).

Administration, Cutaneous↗

Effect of recombinant human transforming growth factor beta 1 on immune responses in patients with chronic hepatitis B.

Studies were undertaken to examine the effect of recombinant human transforming growth factor beta 1 (rTGF-beta 1) on cellular and humoral immune responses of peripheral blood mononuclear cells (PBMC) from patients with chronic hepatitis B. The addition of TGF-beta 1 caused a significant dose-dependent inhibition of hepatitis B (HB) core Ag-stimulated interferon-gamma and antibody to HB core Ag production and proliferation of PBMC from chronic hepatitis patients and HB-immune donors. TGF-beta 1 also induced a significant reduction in pokeweed mitogen-stimulated IgG and IgM production, as well as phytohemagglutinin p-stimulated proliferative response of PBMC. The degree of inhibition of TGF-beta 1 did not differ between antigen-specific and -nonspecific cellular and humoral immune responses, and between control individuals and patients. Pretreatment study with TGF-beta 1 showed that the activities of T cells, B cells and monocytes were similarly inhibited. Further, TGF-beta 1 inhibited activities of HLA class I antigen-matched cytotoxic T cells from patients with chronic hepatitis B for HBV DNA-transfected HepG2 cells in a 51Cr release assay. The results suggest that TGF-beta 1 may play a role in the regulation of antigen-dependent and -independent immune responses in patients with chronic hepatitis B.

Adult↗

Effects of interferon-alpha treatment on hepatitis B virus antigen-specific immunologic responses in patients with chronic hepatitis B.

Studies were undertaken to evaluate the relationship between the immune responses and the effectiveness of interferon-alpha treatment in 21 patients with HBeAg-positive chronic active hepatitis. Peripheral blood mononuclear cells (PBMC), obtained on four occasions during an 8-week course of IFN-alpha therapy, were cultured with recombinant HBcAg, purified HBeAg or pokeweed mitogen (PWM). During follow-up for 6 months after therapy, clearance of serum HBeAg was observed in eight patients designated as responders. Immunological responses of PBMC obtained before treatment did not differ between responders and non-responders. In responders, IFN-gamma and anti-HBc production was depressed during therapy, but recovered to above the pretreatment level at the end of and/or after cessation of therapy, while lymphocyte proliferation was enhanced during therapy with a subsequent decline to baseline value. In non-responders, such changes were modest throughout the study, and anti-HBc response remained decreased even after cessation of therapy. These results indicate that PBMC of responders have immunologically different responses to IFN-alpha therapy when compared with non-responders.

Adolescent↗

In vitro culture of bovine one-cell embryos derived from in vitro fertilization using a semi-chemically defined medium.

The effects of alteration of metabolic substrates and supplementation of amino acids on in vitro development of bovine embryos were examined. One-cell embryos derived from in vitro fertilization were cultured using a semi-chemically defined medium, Brinster's Medium, containing 3 mg/ml bovine serum albumin (BMOC-3) as a basal medium. BMOC-3 did not support embryonic development to the morula stage, but blastocysts were obtained by omitting glucose and lowering the lactate level from 20.12 to 3.0 mM and the pyruvate level from 0.5 to 0.3 mM (mBMOC-3). Supplementation of amino acids (glutamine plus the other 12 essential amino acids, as well as further addition of 7 non-essential amino acids) improved the embryonic developmental rate to the blastocyst stage with an increase in cell number equal to that for co-cultured embryos with bovine oviductal cells in TCM 199 with 10% fetal calf serum. These results clarified that the one-cell bovine embryo can develop to the blastocyst stage in a semi-chemically defined medium, and that amino acids support embryonic development in vitro.

Amino Acids↗

Adult T-cell leukemia involving the central nervous system after remission of adult respiratory distress syndrome.

We report a rare case of adult T-cell leukemia (ATL) in which the patient had an acute type of ATL involving the central nervous system (CNS) after remission of adult respiratory distress syndrome (ARDS) due to human T lymphotropic virus type 1 associated bronchopneumopathy. A 62-year-old woman was admitted to the hospital because of ARDS. Pulse therapy with methylprednisolone improved ARDS, but she fell into a coma due to ATL and CNS invasion 5 months after recovery. Although chemotherapy decreased the fraction of abnormal lymphocytes, her consciousness level did not improve and she died.

Central Nervous System Neoplasms↗

Hormonal disregulation mechanism in the rat thyroid tumor induced by diniconazole.

To assess the toxicological significance of thyroidal tumor observed slightly in a long-term rat study with diniconazole, (E)-1-(2,4-dichlorophenyl)- 4,4-dimethyl-2-(1,2,4-triazol-1-yl)-1-penten-3-ol, a 3-month subacute feeding study was conducted in male Crj: CD (SD) rats by administering diniconazole in diet at concentrations of 0, 100, 1,000, or 2,000 ppm. Examinations mainly for thyroid functions were performed at Weeks 2, 4 and 13. Measurement of serum hormone levels revealed continuous decreases in serum thyroxine (T4) and free T4 levels at and above 1,000 ppm and increase in serum thyroid stimulating hormone (TSH) level at 2,000 ppm concurrently with liver weight and hepatic UDP-glucuronyltransferase (UDP-GT) increases at and above 1,000 ppm. No changes were observed in serum triiodothyronine (T3) and free T3 levels. Increase in thyroid uptake of 125I and organification of 125I in the thyroid at 2,000 ppm and thyroid follicular cell hyperplasia at and above 1,000 ppm were also observed. However, no compound-related changes were observed in autopsy and organ weight in the thyroid. Based on the above results, diniconazole induces increases in the hepatic UDP-GT activity and the thyroid hormone excretion from the liver. The increased excretion of thyroid hormones causes decrease in serum T4 and free T4 levels, triggering the feedback mechanism of the pituitary gland, promotion of TSH release from the pituitary gland and increase in serum TSH level. The increased serum TSH level probably leads to increased 125I uptake of thyroid and thyroid follicular cell hyperplasia. Thus, the thyroid tumorigenesis in rats treated with diniconazole is due to the secondary overstimulant effect on the thyroid by increased serum TSH level. The toxicological significance in humans is extremely low and it is unlikely that diniconazole would increase thyroid tumor in humans even if diniconazole were to alter normal thyroid hormone level in humans.

Animals↗

Nephrotic syndrome with massive accumulation of type I and type III collagen in the glomeruli.

A 54-year-old woman with nephrotic syndrome underwent renal biopsy. By light microscopy, the glomerular capillary lumen was remarkably narrowed because of diffuse accumulation of Periodic acid Shiff (PAS) positive material along the glomerular capillary wall. By electron microscopy, collagenous fibers were observed in the mesangium and subendothelial area. The fibrous material reacted with antibodies against type I and III collagen but not with those against laminin or type IV collagen by an indirect immunofluorescence technique. This case seemed to be a case of collagenofibrotic glomerulonephropathy.

Collagen↗

Cytomegalovirus mononucleosis with mixed cryoglobulinemia presenting transient pseudothrombocytopenia.

A 61-year-old man was admitted to our hospital because of fever and general malaise. We diagnosed his condition as cytomegalovirus (CMV) mononucleosis by hematological testing. His platelet count was decreased in spite of collection with several anticoagulants at room temperature (20 degrees C); no decrease was observed at 37 degrees C. Mixed cryoglobulinemia, monoclonal IgM and polyclonal IgG, which acted as anti-platelet antibodies in cold condition, were found in the patient's serum. With the resolution of CMV infection, the cryoglobulins disappeared and the platelet count returned to normal without platelet agglutination. This is the first report of transient pseudothrombocytopenia in CMV mononucleosis with mixed cryoglobulinemia.

Antigens, Human Platelet↗

[Expression of fibronectin receptor and vitronectin receptor in diseased human kidneys].

Expression of fibronectin and vitronectin receptors was studied in normal human kidney tissues and renal tissue biopsies from patients with several types of glomerulonephritis. Immunofluorescent staining of the normal kidneys showed that fibronectin receptor was present along the glomerular capillary walls, and that vitronectin receptor was present in the vessel walls, but was almost absent from the glomerulus. In kidney tissues biopsied from patients with various renal diseases, expression of fibronectin and vitronectin receptors was correlated with increase in the mesangial expansion. Expression of these receptors was decreased in the sclerosed area and hyalinized glomeruli compared with normal tissues. Fibronectin and vitronectin receptors were occasionally colocalized in the glomeruli with fibronectin and vitronectin, respectively. In situ hybridization showed that fibronectin receptor mRNA and vitronectin receptor mRNA were expressed in the diseased glomeruli. These findings indicate that expression of fibronectin and vitronectin receptors was altered in human glomerulonephritis, and that integrin expression may be important in cell-matrix interaction in the diseased glomeruli.

Glomerulonephritis↗

[A newly-devised nine-lead Holter system for diagnosing myocardial ischemia evaluated using Tl-201 exercise scintigraphy].

A 9-lead Holter monitoring apparatus was devised using a commercially-available 3-lead Holter recorder. The CM5 lead was monitored continuously on channel 1, and our apparatus was applied to channels 2 and 3. Channel 2 was switched serially to V1-like (CM1), V4-like (CM4), V2-like (CM2) and V3-like (CM3) leads every 20 sec. Channel 3 was switched serially to V6-like (CM6), low-back (LB), high lateral (HL) and low-lateral (LL) leads every 20 sec. The study subjects included 98 patients with coronary artery disease. Myocardial ischemia was evaluated by exercise thallium-201 (Tl-201) scintigrams. Functional maps of myocardial perfusion were made from Tl-201 myocardial SPECT studies, and the extent and severity scores were calculated from these maps. The CM5 lead had a high sensitivity for detecting anterior, inferior and lateral wall ischemia, however, its specificity was very low. In contrast, the LB lead had very high sensitivity and high specificity for detecting inferior ischemia (79%, 76%, respectively). The percent extent score and percent severity score determined by the bull's eye method were compared between patients with ST depression of 0.5-1.0 mm and those with that greater than 1.0 mm detected by the LB lead. Both the percent extent score and percent severity score in the latter group were significantly higher than those in the former group (p < 0.001, p < 0.01, respectively), suggesting that the degree of ST depression in the LB lead reflects the degree of myocardial ischemia. The HL and LL leads had high sensitivity and specificity for detecting lateral ischemia. It was concluded that the CM5 lead is necessary for screening global myocardial ischemia and that leads LB and HL (or LL) are mainly useful for detecting inferior and lateral ischemia.

Coronary Disease↗

Electrochemical assay system with single-use electrode strip for measuring lactate in whole blood.

We have developed an assay system for measuring lactate in whole blood, consisting of a single-use strip of an enzyme-coated electrode and a small meter. The electrode strip is made of three plastic films: a cover sheet, a spacer, and an insulation layer printed with electrodes that are coated with lactate oxidase (EC 1.1.3.x) and ferricyanide as an electron mediator. The meter measures the magnitude of the anodic current of the reduced mediator by the enzymatic reaction and displays the lactate concentration 60 s after a blood sample (5 microL) is applied. The calibration curve was linear up to 20 mmol/L, and the between-run CVs at three concentrations were 1.7-8.4%. Lactate concentrations determined by this method (y) in blood samples from healthy individuals before and after exercise agreed with the results obtained by the conventional enzymatic method (x): y = 0.97x - 0.3, Sy/x = 0.7. This assay provides a rapid and convenient test for measuring blood lactate concentrations.

Biosensing Techniques↗

Relative immunogenicity of hepatitis B virus-encoded antigens as targets for cytotoxic T-cell response.

To analyse the immunological mechanism of hepatocellular injury in hepatitis B virus (HBV) infection, the immunoreactivity of HBV-encoded antigens as a target for cytotoxic T lymphocyte (CTL) response was examined using recombinant vaccinia virus (RVV) expressing surface protein (S), precore/core protein (PC), and core protein (C) of HBV. C3H/He mice (H-2k) were inoculated with each RVV. Their spleen cells were then harvested and stimulated in vitro with the histocompatible transfectant, which stably expressed hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core antigen (HBcAg), and used as effectors. As the targets, L cells (H-2k) infected with individual RVV were used. Cytotoxic test was performed with various combinations and ratios of effectors and targets. The reactivity of PC-primed effectors against PC-expressing targets was greatest with 71.4% specific lysis on average at an effector/target ratio of 12.5:1 among all the combinations. C-primed effectors against C-expressing target also revealed rather high cytotoxicity (specific lysis, 40.6% at an E/T ratio of 12.5:1). Furthermore, PC-primed and C-primed effectors showed a cross-reactivity to the targets expressing other nucleocapsid antigen, respectively. S-primed effectors showed less lytic activity against S-expressing targets (specific lysis, 18.4% at an E/T ratio of 12.5:1). The CTL responses were blocked by anti-CD8 and anti-major histocompatibility complex (MHC) class I antibodies, but not by anti-CD4 or anti-MHC class II. These findings suggest that endogenously synthesized nucleocapsid antigen, especially PC, is a dominant target for the MHC class I-restricted CTL in H-2k mice and that this system may work as an efficient model to study immunopathogenesis of HBV infection.

Animals↗

[Mechanism of tumor cell invasion studied by a culture model--modification of invasiveness by host mediators].

A culture model for invasion of rat mesothelial cell layer by rat ascites hepatoma cells has been developed. By using this quantitative model, we have recently found that the invasiveness of tumor cells is not only genetically determined but is greatly influenced by their interactions with host cells and host mediators. The preculture with macrophages was found to enhance both the in vitro and in vivo invasive potentials of the tumor cells. This potentiation appears to be mediated partly by oxygen radicals generated by the cocultured macrophages. The in vitro invasive capacity was also augmented by pretreating the tumor cells with TGF-beta, or with activated platelets. In the in vitro invasion assay system, tumor cells did not invade against cultured mesothelial cell monolayers without fetal calf serum. Serum could be completely substituted by oleoyl-lysophosphatidic acid (LPA) or bacterial phospholipase D (PLD), suggesting a possible participation of particular signaling cascade, PLD-LPA(PA) system, in the invasion of certain tumor cells.

Animals↗