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Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 523 records · Page 29Linked to original sources

Interleukin-10 inhibited the expression of tumor antigens and major histocompatibility complex antigen on EJ-ras oncogene transformants.

Interleukin-10 (IL-10), a novel inhibitory cytokine, is one of Th-2 (T helper) cytokine. It inhibits mixed lymphocyte reaction, and the production of inflammatory cytokine and monokine downregulates major histocompatibility complex antigen (MHC) class II antigen expression. However, the effect of IL-10 on tumor cells is not known. Therefore, the mechanism of tumor tolerance induced by IL-10 was investigated. (WKA rat fetus-derived fibroblast) (WFB) and W14 and W31 (EJ-ras oncogene transformants of WFB) were cultured with recombinant human (rh)IL-10 (0, 10, 50, 100 ng/ml). FACS analysis was performed using the following monoclonal antibodies: anti-rat MHC class I monoclonal antibody; and monoclonal antibody 109 (anti-natural killer [NK] target molecule on W14). Monoclonal antibody (mAb) 109-defined antigens were newly expressed during the transforming process by EJ-ras oncogene transfection to WFB. In addition, the effects of rhIL-10 on the ability of proliferation and susceptibility to NK cells were assessed. The cultivation with rhIL-10 resulted in a dose-dependent decrease in the expressions of MHC class I antigen and monoclonal antibody 109-defined antigen. The proliferation and susceptibility to NK cells of W14 were inhibited. These data demonstrated a possibility that IL-10 could induce tumor tolerance to host immunity by inhibiting the expression of tumor-associated antigens and MHC class I.

Animals↗

Treatment of children with congenital heart disease and growth retardation with recombinant human growth hormone.

Seven prepubertal short children with congenital heart disease were treated with recombinant human growth hormone (GH). Although complete surgical correction was performed for their heart disease at least 2 years before the start of GH therapy, improvement in growth was less than expected in these children. They received 0.5 IU kg-1 week-1 of GH daily for 2 years or more. The growth rate increased from a mean of 4.3 cm year-1 before treatment to a mean of 7.8 cm year-1 in the first year and to a mean of 6.3 cm year-1 in the second year of treatment. Their mean standardized height improved from -3.41 +/- 0.78 to -2.54 +/- 0.62 after 2 years. The mean height age difference minus the bone age difference became positive in these children. We conclude that recombinant GH increases the growth rate in children with congenital heart disease and prepubertal growth retardation.

Child↗

Antiubiquitin antibody in localised and systemic scleroderma.

OBJECTIVE: To determine the presence of antiubiquitin antibody (AUbA) in localised scleroderma and systemic sclerosis, as it is frequently found in the sera of patients with systemic lupus erythematosus (SLE) and has also been shown to have a close relationship with antihistone antibodies that have an important role in scleroderma. METHODS: Serum samples from patients with localised scleroderma (n = 48) and systemic sclerosis (n = 52) were examined by enzyme linked immunosorbent assay. Twenty samples from patients with SLE, 20 from patients with dermatomyositis, and 30 samples from healthy individuals were used as controls. RESULTS: AUbA was demonstrated in 44% of patients with localised scleroderma and in 42% of those with systemic sclerosis. The presence of AUbA correlated with the presence of antihistone antibodies in both localised scleroderma and systemic sclerosis. CONCLUSIONS: AUbA is frequently present in patients with localised scleroderma and systemic sclerosis. Induction of AUbA is closely associated with that of antihistone antibodies, suggesting that ubiquitinated histone may be the target in autoimmune responses of these disorders.

Adolescent↗

Expression of hybrid isomyosins in human skeletal muscle.

Myosin of human skeletal muscles was analyzed by means of several electrophoretic techniques. Myosin heavy chain (HC)-IIa-and HC-IIb-based isomyosins were identified by pyrophosphate-polyacrylamide gel electrophoresis (PP-PAGE). The electrophoretic mobilities of these fast-twitch muscle isomyosins differed in the order HC-IIa triplets < HC-IIb triplets. To determine the subunit composition of myosin molecules that function in intact muscle, two-dimensional electrophoresis in which the first and second dimensions were PP-PAGE and sodium dodecyl sulfate-PAGE, respectively, was also performed. Slow-twitch muscle isomyosin contained, in addition to slow-twitch light chain (LC) and HC-I isoforms, appreciable amounts of LC-2f, HC-IIa, and HC-IIb isoforms, and fast-twitch muscle isomyosin consisted of LC-2s and HC-I isoforms as well as fast-twitch LC and HC isoforms. Without consideration of HC- and slow-twitch alkali LC heterodimers, at least 31 possible isomyosins are derived from these findings on the subunit composition of isomyosins in human skeletal muscle.

Diphosphates↗

Nitric oxide release from kidneys of hypertensive rats treated with imidapril.

To examine whether endothelial dysfunction in hypertension is reversible or not, we studied the effects of imidapril, an angiotensin-converting enzyme inhibitor, on nitric oxide release in stroke-prone spontaneously hypertensive rats (SHR) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. After a 4-week treatment with imidapril (1 or 10 mg/d SC) or vehicle, acetylcholine-induced vasodilation and nitric oxide release in the isolated kidneys were determined. Nitric oxide release was measured by a chemiluminescense assay. Imidapril lowered blood pressure in stroke-prone SHR in a dose-dependent manner. Untreated stroke-prone SHR exhibited significantly attenuated responses to acetylcholine (10(-8) mol/L) of both renal perfusion pressure (stroke-prone SHE 42 +/- 4% versus Wistar-Kyoto rats [WKY] 58 +/- 4% [mean +/- SE], P < .01) and nitric oxide release (stroke-prone SHR +7.6 +/- 2.1 versus WKY +29.7 +/- 9.7 fmol/min per gram of kidney wt, P < .01). Imidapril at 10 mg/d significantly increased acetylcholine-induced renal vasodilation and nitric oxide release in stroke-prone SHR (renal perfusion pressure, 56 +/- 3%; nitric oxide release, +27.1 +/- 6.4 fmol/min per gram of kidney wt; both P < .01 versus stroke-prone SHR treated with vehicle). On the other hand, imidapril neither decreased blood pressure nor changed nitric oxide release induced by acetylcholine in DOCA-salt hypertensive rats. Staining for endothelial nitric oxide synthase and brain nitric oxide synthase was clearly detected in the kidneys of both stroke-prone SHR and WKY, whereas staining intensity was weaker in DOCA-salt hypertensive rats. Inducible nitric oxide synthase immunoreactivity was barely noticeable in any type of rat. Thus, imidapril restored endothelial damage by pressure-dependent mechanisms. Most of the nitric oxide detected in the perfusate seemed to be derived from constitutive nitric oxide synthase.

Angiotensin-Converting Enzyme Inhibitors↗

Demonstration of the nasal septal branches of the sphenopalatine artery by use of a new intravascular injection method.

We injected a new injection material into the external carotid artery using a new method, which led to the successful demonstration of the nasal septal branches of the sphenopalatine artery in human cadavers. The result shows the trunk of the artery divided into three main branches, the upper two of which run toward Little's area. We believe that the knowledge of septal branches, shown in a photograph, is very useful, not only for nasal treatment, but also for anatomic demonstration to students.

Aged↗

Pharmacokinetics of tamsulosin hydrochloride in patients with renal impairment: effects of alpha 1-acid glycoprotein.

The pharmacokinetics of tamsulosin hydrochloride in patients with renal impairment were compared with those in healthy volunteers, and the factors that influenced plasma levels of tamsulosin were elucidated. A single oral dose of 0.2 mg of tamsulosin was given and blood and urine samples were obtained for 36 hours after administration. Unbound plasma concentration of tamsulosin was measured by a combination of equilibrium dialysis and liquid chromatography tandem mass spectrometry methods to examine the effect of protein binding on the pharmacokinetics of tamsulosin. Mean values for maximum concentration (Cmax) and area under the concentration-time curve (AUC) of total drug (Cmax,t and AUC1) in patients with renal impairment were 73% and 211% greater, respectively, than those in healthy volunteers. Mean Cmax and AUC of unbound drug (Cmax,u and AUCu), however, were almost the same in the two groups. A high correlation was found between alpha 1-acid glycoprotein (alpha 1-AGP) concentration and AUCt, but no correlation was found between alpha 1-AGP concentration and AUCu,0-36) or between creatinine clearance (ClCR) and AUCu,0-36). These results show that in patients with renal impairment, the pharmacokinetics of tamsulosin are affected by the change in protein binding that is associated with alteration of plasma alpha 1-AGP concentration, but are not largely affected by the decrease in the renal excretion. Although total tamsulosin levels increased as plasma protein binding increased, unbound tamsulosin levels (which are directly associated with the pharmacologic effects) remained unchanged in these patients.

Adrenergic alpha-Antagonists↗

CTG repeat size and histologic findings of skeletal muscle from patients with congenital myotonic dystrophy.

An approximate correlation has been demonstrated between the degree of CTG repeat expansion and clinical severity among myotonic dystrophy patients. Congenital myotonic dystrophy, which is the most severe form of the disease, has the largest size of CTG repeat. Muscle immaturity is a characteristic finding in congenital myotonic dystrophy muscle. We compared the CTG repeat size and histologic findings of skeletal muscle from patients with congenital myotonic dystrophy. An 8.6 kb or 9.8 kb plus an expanding band ranging from 15 kb to 17.5 kb was observed in muscle from five patients with congenital myotonic dystrophy by Southern blot analysis using EcoRI-digested DNAs probed with p5B1.4. There was no correlation between immaturity of skeletal muscle and the degree of CTG repeat expansion on skeletal muscle. Undetermined maternal factors may have an important role in the cause of immaturity of muscle in congenital myotonic dystrophy patients.

Blotting, Southern↗

Effects of thyroid hormone on carbonic anhydrase I concentration in human erythroid burst-forming unit-derived cells.

Individuals with hyperthyroidism exhibit red blood cell concentrations of carbonic anhydrase I (CAI) that reflect the integrated serum thyroid hormone concentration over the preceding few months. Furthermore, T3, at a physiological free concentration, decreases the CAI concentration in human erythroleukemic YN-1 cells. The effect of T3 on CAI concentration in burst-forming unit-erythroid (BFU-E)- derived cells, obtained by culturing peripheral blood mononuclear cells with various cytokines, including erythropoietin, has now been investigated. BFU-E-derived cells contained a high concentration of CAI (mean +/- SE, 4.8 +/- 0.8 x 10(-12) mol/10(6) cells; n = 8). The CAI in BFU-E-derived cells was immunologically identical to that present in mature red blood cells. T3 decreased the CAI concentration in BFU-E-derived cells in a dose-dependent manner (28%, 47% and 75% decreases at 3 x 10(-10), 1 x 10(-9), and 3 x 10(-9) mol/liter T3, respectively). These results suggest that BFU-E-derived cells may be used to study the effect of T3 on human red blood cell CAI. This system may prove useful in the tissue diagnosis of resistance to thyroid hormone.

Adult↗

Novel detection method of nitric oxide using horseradish peroxidase.

Nitric oxide (NO) readily makes corresponding complexes not only with ferrous iron but also with ferric iron. However, NO-ferric complexes of many heme proteins were unstable, while horseradish peroxidase formed the very stable NO-ferric porphyrin complex with a shift of the Soret band of the absorption wavelength from 396.5 nm to 420.0 nm. The concentration of NO in aqueous media could be monitored by measuring the absorption changes, and the detection limit was 10 nM. The simple procedure is convenient for concentration determination of NO solution.

Calibration↗

Antioxidant effects of calcium antagonists on rat myocardial membrane lipid peroxidation.

We studied the antioxidant effects of nine calcium antagonists (nisoldipine, benidipine, nilvadipine, felodipine, nicardipine, nitrendipine, nifedipine, verapamil, and diltiazem) by means of rat myocardial membrane lipid peroxidation with a nonenzymatic active oxygen-generating system (DHF/FeCl3-ADP). The order of antioxidant potency of these agents was nilvadipine > nisoldipine > felodipine > nicardipine > verapamil > benidipine. Their IC50 values (microM) were 25.1, 28.2, 42.0, 150.0, 266.1, and 420.0, respectively. In contrast, nitrendipine, nifedipine, and diltiazem had little inhibitory effect on lipid peroxidation. These six calcium antagonists could be divided into four types on the basis of their antioxidant mechanisms. Nilvadipine, nisoldipine, and verapamil, which showed antioxidant effects both before and after the addition of active oxygen, and reduced the dihydroxyfumarate (DHF) auto-oxidation rate, were chain-breaking and preventive antioxidants. Felodipine, which showed antioxidant effects both before and after exposure to active oxygen and increased the DHF auto-oxidation rate, was only a chain-breaking antioxidant. Nicardipine, which showed an antioxidant effect only before exposure to active oxygen and reduced the DHF auto-oxidation rate, was mainly a preventive antioxidant. Benidipine, which showed an antioxidant effect only before exposure to active oxygen and had no appreciable effect on the DHF auto-oxidation rate, could interrupt the chain reaction of lipid peroxidation at the initial step alone. Although these results suggest that the antioxidant properties of some calcium antagonists may be beneficial clinically in protecting against cellular damage caused by lipid peroxidation, further studies are required to establish the antioxidant effects of these agents in vivo.

Adenosine Diphosphate↗

Distribution of amyloid bodies in the aged human vestibulocochlear nerve.

We tried to elucidate the localization and distribution of amyloid bodies (Corpora amylacea) in the human vestibulocochlear nerve stained with luxol fast blue-periodic acid Schiff-hematoxylin using of a combination of an image analyzing computer system and a microscope fitted with a drawing tube. After having observed each section of the vestibulocochlear nerve from the brain stem to the fundus of the internal auditory meatus, we counted the numbers of amyloid bodies in three different parts for each of three corpses, and measured the areas. We found that amyloid bodies of the vestibulocochlear nerve are concentrated to the limiting glial portion of the nerve more than to the nerve parenchyma, and amyloid bodies are not seen in the vestibulocochlear nerve peripheral to the transitional zone. Our quantitative trial proved that the amyloid body was larger in the 8th decade than in the 6th or 7th decade of life.

Aged↗

Antibody catalysis via strategic use of haptenic charge.

General acid-base catalysis contributes substantially to the efficacy of many enzymes. Similar effects can be exploited in antibody catalysis by taking advantage of charge complementarity between immunoglobulin and hapten (the template used to induce the antibody) to elicit functional groups in the combining site. This strategy has proved useful in the catalysis of a diverse set of chemical transformations, including elimination reactions. Provided that hapten design is optimized and the immune response is screened extensively, the efficiency of the resulting antibody catalysts can rival that of analogous natural enzymes.

Alkenes↗

Titration of human cytomegalovirus (HCMV) DNA in urine by combined use of PCR and microplate hybridization in a renal transplant patient with HCMV pneumonitis.

We titrated human cytomegalovirus (HCMV) DNA in urine specimens obtained from 14 healthy individuals and a renal transplant patient with HCMV pneumonitis by modifying the method for titration of varicella-zoster virus DNA previously described (1,2). Of 14 HCMV seropositive healthy individuals, 13 had HCMV DNA under the detection limit of 10(2.0) copies/ml, whereas one person had 10(2.0) copies/ml. The viral DNA in urine samples was at a low level in healthy individuals with latent infection. In a case with HCMV pneumonitis after renal transplantation, the amount of HCMV DNA in urine gradually increased from the level under 10(2.0) copies/ml and reached a peak of 10(4.7) copies/ml one month prior to the manifestation of pneumonitis. It, thereafter, decreased with the course of clinical remission, and finally settled at under 10(2.0) copies/ml. Serial titrations of HCMV DNA in urine specimens proved to be useful in identifying recipients at risk of developing active HCMV infection after renal transplantation and as a guide for treatment of patients.

Cytomegalovirus↗

[Comparison of clinical effects between granisetron alone and combination of granisetron and methylprednisolone against the nausea and vomiting induced by CDDP chemotherapy--comparative study by the cross-over trial. University of Tsukuba Antiemetics Study Group].

A cross-over clinical trial was carried out to compare the antiemetic effect and safety between granisetron alone (40 micrograms/kg) and the combination of granisetron and methylprednisolone (MP: 10 mg/kg) in urological cancer patients treated with cisplatin. Forty-eight courses were given with granisetron alone and 47 courses with both granisetron and MP. The antiemetic effect of nausea and vomiting was evaluated in the acute emetic phase. during the 24 hours following the CDDP administration, and in the delayed emetic phase, 2 to 7 days after the administration. Combination therapy of granisetron and MP demonstrated a greater antiemetic effect during the 72 hours following the CDDP administration than by granisetron alone. But there was no significant difference in antiemetic effect between combination therapy and granisetron alone after the 3rd day. Combination therapy also demonstrated more efficacy in complete antiemetic effect, with no emesis and less than moderate nausea, than by granisetron alone. Both treatments showed no side effects and were safe.

Aged↗

[Reconstruction of chest wall defects with autogenous ribs grafts].

Three methods of chest wall reconstruction using autogenous rib grafts were reported. Fresh non-vascularized autogenous rib graft, vascularized autogenous ribs with muscle-flap, and pasteurized autogenous rib grafts were the materials used in these techniques. They are less convenient than those with artificial materials but afterwards physiologically more natural chest wall will be reconstructed. The third method (pasteurized rib graft) was applied to 22-year-old female with large recurrent desmoid tumor. Six resected ribs were heated in the saline at 60 degrees C for 30 min. and three of them were returned to the former position. Though tumor cells and bacteria are killed under this condition, these heated bone can be revascularized and replaced by normal bone as early as fresh non-vascularized rib graft.

Adult↗