Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 109 records · Page 6Linked to original sources

PubMed2001

Visualization of oxygen-concentration-dependent production of nitric oxide in rat hippocampal slices during aglycemia.

Our novel fluorescent indicator, DAF-FM, permits the bioimaging of nitric oxide (NO) in living cells with high resolution in space and time, with stable intensity above pH 5.8. A membrane-permeable derivative, DAF-FM DA, was applied to imaging of NO generated in rat hippocampal slices by exposure to an aglycemic medium. NO production was observed mainly in the CA1 area, and was dependent on the concentration of O(2). During exposure to an anoxic-aglycemic medium, NO was hardly produced, while marked elevation of intracellular Ca(2+) was observed. Production of NO increased sharply as soon as the perfusate was changed to the normal medium. These results suggest that NO synthase is activated after reperfusion rather than during ischemia.

Animals↗

PubMed2001

Changes of cytokines in direct endotoxin adsorption treatment on postoperative multiple organ failure.

Multiple organ failure (MOF) is a serious condition that involves simultaneous or consecutive functional failure of several important organs. Furthermore, sepsis is known to play an important role in the occurrence of MOF. Hemoadsorption therapy with the endotoxin adsorption column containing polymyxin B immobilized fibers by direct hemoperfusion (PMX-DHP) is reportedly effective in the treatment of septic shock. This study examined the changes induced on cytokines upon PMX-DHP treatment in 25 patients who underwent emergency abdominal surgery and were immediately started on a postoperative regimen of continuous hemodiafiltration (CHDF) and PMX-DHP. Postoperative MOF was observed in these patients with a mean APACHE II SCORE of 25.5. Eighty percent of patients survived for more than 1 month. We were able to reduce the necessary dose of dopamine in 85.7% of patients because hemodynamic stability improved after administration of PMX-DHP. Interleukin 6 blood levels did not change significantly before or after PMX-DHP treatment in either the surviving or nonsurviving patients. Blood interleukin 1 receptor antagonist levels decreased in both groups. Intercellular adhesion molecular-1, NOx, and thrombomodulin did not change significantly during the course of treatment in either group. Decreased blood levels of PAI-1 levels were found in the surviving patients whereas increased levels of PAI-1 were found in the non-surviving patients. In conclusion, PMX-DHP treatment may be limited clinically in its ability to remove inflammatory cytokines and humoral mediators. However, PMX-DHP treatment is useful for hemodynamic stabilization, which prevents development of MOF.

APACHE↗

PubMed2001

Outcomes of hemodiafiltration based on Japanese dialysis patient registry.

Effectiveness of various therapeutic modalities was analyzed among 1,196 patients entered in the registry of the Japanese Society for Dialysis Therapy who were on hemopurification therapy as of the end of 1998 and developed dialysis-related amyloidosis during 1999. In the investigation, the effectiveness of various hemopurification modalities on the dialysis-related amyloidosis was ranked as exacerbation, unchanged, or alleviation, so as to analyze the possible relationship between the hemopurification modality and its effectiveness. The analysis was performed using a logistic regression approach, and the results were shown as "the risk of a worse therapeutic ranking" among the hemopurification modalities. The smaller "the risk of a worse therapeutic effect" was, the more effective the treatment modality. When the risk of a worse therapeutic effect for the hemodialysis patients treated by a regular membrane was put at 1.0, the risk for hemodialysis patients using high-flux membrane was 0.489, the off-line hemodiafiltration risk was 0.117, the on-line hemodiafiltration risk was 0.013, and the risk of push/pull hemodiafiltration was 0.017. For hemodialysis with a beta(2)-microglobulin adsorption column, a low risk of 0.054 was found. The results indicated that hemodiafiltration therapy and simultaneous hemodialysis with beta(2)-microglobulin adsorption therapy were more effective treatment for dialysis-related amyloidosis.

Amyloidosis↗

PubMed2001

Detection of antimitochondrial autoantibodies in immunofluorescent AMA-negative patients with primary biliary cirrhosis using recombinant autoantigens.

Antimitochondrial antibodies (AMA) are the serologic hallmark of primary biliary cirrhosis (PBC). However, depending on the clinical laboratory, from 5% to 17% of PBC patients are consistently AMA-negative, using native mitochondrial antigens and a variety of conventional assays including immunofluorescence (IMF) and enzyme-linked immunosorbent assay (ELISA). The major immunoreactive mitochondrial autoantigens are the E2 members of the 2-oxo-acid dehydrogenase complex family, including pyruvate dehydrogenase complex-E2 (PDC-E2), branched chain 2-oxo acid dehydrogenase complex-E2 (BCOADC-E2), and oxo-glutarate dehydrogenase complex-E2 (OGDC-E2); cDNAs of these proteins have now been cloned, sequenced, and their B-cell epitopes defined. In the present study, we cloned cDNAs encoding these proteins from human, not bovine, sources, and expressed the recombinant proteins in a newly developed ELISA that employs a unique Escherichia coli buffer, and compared the data with previous assays using both AMA-positive and -negative patients. Using this new assay and our criteria for positive as an optical density (OD) greater than 10 SD above the mean of control sera, the AMA-positive rate of 191 PBC sera was 94% (179 of 191) compared with 84% (161 of 191) by IMF. None of the 316 control sera were reactive. Using our recombinant assays, we focused attention on the 30 IMF-AMA-negative patients. Twenty-two of 30 (73%) of these patients were positive using this new ELISA. The group of 30 IMF-AMA-negative/ELISA-positive patients did not differ significantly from a comparable population of IMF-AMA-positive patients with respect to age, sex distribution, liver function tests, elevation of serum IgM, or pathologic stage.

Autoantibodies↗

PubMed2001

A case of familial atrioventricular heart block affected by alteration of the autonomic nervous system.

Familial atrioventricular heart block affected by the autonomic nervous system has rarely been documented. We describe a 35-year-old man who had first-degree atrioventricular heart block with a PR interval of 0.46 s. He had a family history of 2 members with complete heart block and 1 with documented atrial standstill. The man's P-R interval was shortened by exercise and phenylephrine administration. In the electrophysiolgic study, a "split His" with an H-H' of 220 ms was recognized. Such a case of familial atrioventricular heart block with abnormal His-Purkinje conduction affected by the autonomic nervous system is very rare and worthy of description.

Adult↗

PubMed2001

Recurrent septicemia caused by Streptococcus canis after a dog bite.

Human infection with Streptococcus canis is extremely rare. We describe herein a case of septicemia with cellulitis caused by S. canis in a 75-y-old woman, which developed 2 weeks after a dog bite. Macrorestriction analysis with pulsed-field gel electrophoresis demonstrated that the organism had been transmitted by means of a dog bite to her hand.

Aged↗

PubMed2001

An anisotropic diffusion method for denoising dynamic susceptibility contrast-enhanced magnetic resonance images.

The purpose of this study was to present an application of a novel denoising technique for improving the accuracy of cerebral blood flow (CBF) images generated from dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI). The method presented in this study was based on anisotropic diffusion (AD). The usefulness of this method was firstly investigated using computer simulations. We applied this method to patient data acquired using a 1.5 T MR system. After a bolus injection of Gd-DTPA, we obtained 40-50 dynamic images with a 1.32-2.08 s time resolution in 4-6 slices. The dynamic images were processed using the AD method, and then the CBF images were generated using pixel-by-pixel deconvolution analysis. For comparison, the CBF images were also generated with or without processing the dynamic images using a median or Gaussian filter. In simulation studies, the standard deviation of the CBF values obtained after processing by the AD method was smaller than that of the CBF values obtained without any processing, while the mean value agreed well with the true CBF value. Although the median and Gaussian filters also reduced image noise, the mean CBF values were considerably underestimated compared with the true values. Clinical studies also suggested that the AD method was capable of reducing the image noise while preserving the quantitative accuracy of CBF images. In conclusion, the AD method appears useful for denoising DSC-MRI, which will make the CBF images generated from DSC-MRI more reliable.

Aged↗

PubMed2001

Suppression of thymic development by the dominant-negative form of Gads.

Gads, a hematopoietic-lineage-specific Grb2 family member, is involved in the signaling mediated by the TCR through its interactions with SLP-76 and LAT. Here, we generated transgenic mice expressing Grf40-dSH2, an SH2-deleted dominant-negative form of Gads, which is driven by the lck proximal promoter. The total number of thymocytes was profoundly reduced in the transgenic mice, whereas in the double-negative (CD4(-)CD8(-)) thymocyte subset, in particular the CD25(+)CD44(-) pre-T cell population, it was significantly increased. However, CD5 expression, which is mediated by pre-TCR stimulation, was significantly suppressed on the CD4(-)CD8(-) thymocytes of the transgenic mice. Furthermore, the SLP-76-dependent signaling was markedly suppressed as well. These data suggest that Gads plays an important role in the pre-TCR as well as TCR signaling in thymocytes.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Construction of the dual-functional RNA ligand against HCV NS3 protease and helicase.

Non-structural protein 3 (NS3) of hepatitis C virus (HCV) contains two distinct activities, protease and helicase which are essential for the HCV replication. In the previous study, we succeeded to obtain RNA aptamers, G9-I, G9-II and G9-III specific for the NS3 protease domain (delta NS3) by in vitro selection (1). As the result of mutational analysis in G9-I, we could obtain the minimum length of RNA structure, delta NEO-III maintaining the full inhibitional activity as shown in G9-I. Furthermore, we created a bi-functional novel RNA ligand, NEO-III-14U which was constructed by connecting delta NEO-III with (U)14 at the 3' terminal. NEO-III-14U was able to inhibit the unwinding of duplex DNA catalyzed by the Full-NS3 helicase activity as well as the protease activity in vitro. Consequently, we could obtain the dual-functional RNA ligand which could inhibit both NS3 protease and helicase activities essential for the HCV proliferation.

Base Sequence↗

PubMed2001

Production and endocrine role of inhibin during the early development of bull calves.

This study investigated the ontogeny of control of FSH secretion by inhibin during early prepubertal development of bulls by 1) measurements of circulating levels of inhibin and FSH from 1 to 13 wk of age, and 2) immunoneutralization of endogenous inhibin at 7, 21, 60, and 120 days of age. In addition, production and localization of inhibin in testes were examined by immunohistochemistry and Western blots at 7, 21, 60, and 120 days of age. Plasma immunoreactive inhibin levels were relatively low between 1 and 3 wk of age and then showed a tendency to rise (P < 0.1) from 4 wk of age. Circulating concentrations of FSH were low during 3 wk after birth and increased at 5 wk, remained high (P < 0.05) until 16 wk of age. Treatment with inhibin antiserum resulted in a significant (P < 0.05) increase in plasma FSH at 7, 21, 60, and 120 days of age compared to those following injection of control serum; however, the magnitude of the FSH rise after inhibin immunization was greater as bulls aged. There were no significant changes in plasma LH after inhibin immunization. An intense staining of inhibin alpha subunits was found in Sertoli cells within the solid seminiferous cords from 7 to 120 days of age, while no specific immune reaction was found in interstitial cells. Western blot analysis of testicular homogenates isolated from bulls 7-120 days of age revealed presence of a 28.5-kDa molecule that cross-reacted with inhibin alpha subunit and beta(B) subunit-specific antibodies. In this study, before 13 wk of age in bull calves, there was no inverse relationship between plasma concentrations of immunoreactive inhibin and FSH. However, the present immunization study clearly indicates that inhibin participates in the regulation of FSH secretion from infancy to early prepubertal stage, although the endocrine significance of inhibin becomes greater in older bulls. The results also indicate that the major production site of inhibin in the testis is Sertoli cells and that these cells produce inhibin that exerts a negative feedback effect on FSH secretion from early stages of development.

Aging↗

PubMed2001

The anesthetic management of a patient with hemoglobin M(Iwate).

IMPLICATIONS: Pulse oximetry is now considered essential for anesthetic management. We treated a patient with hemoglobin M(Iwate), a rare inheritable hemoglobinopathy rendering pulse oximetry completely useless because of its anomalous absorption spectrum.

Anesthesia, General↗

PubMed2001

Intense uptake of technetium-99m tetrofosmin by lactating breasts.

A 38-year-old woman was hospitalized for syncope. Because an electrocardiogram showed intermittent ventricular tachycardia, myocardial perfusion imaging with technetium-99m tetrofosmin was performed to screen for coronary artery disease. Left ventricular myocardial perfusion was within normal limits. However, symmetric bilateral breast uptake was noted. According to her clinical history, she had been breast-feeding her 5-month-old infant until this admission. In these circumstances, the breast uptake of Tc-99m tetrofosmin was thought to be physiologic and related to lactation.

Adult↗

PubMed2001

Effects of angiotensin converting enzyme inhibitor and angiotensin II type 1 receptor blocker on cardiac dysfunction induced by isoproterenol in dogs.

We examined whether angiotensin converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor blockers (ARB) prevent isoproterenol (ISO)-induced left ventricular (LV) dysfunction in dogs. The effects of a large dose of ISO, 1 microg/kg/min, 3 h infusion, were investigated in three groups with simultaneous infusion of an ACE inhibitor (quinaprilat), ARB (candesartan) or saline. ISO infusion significantly decreased LV dP/dt, LV ejection fraction and LV fractional shortening, and significantly increased tau, the time constant of isovolume relaxation of LV, and LV end diastolic pressure. All of these changes were significantly attenuated in both the ACE inhibitor and ARB groups, especially in the ARB group. Serum levels of creatinin kinase isoform MB, lactate dehydrogenase and lipid peroxide were significantly increased by ISO. However, the increases in these markers of myocardial damage were significantly diminished by simultaneous infusion of an ACE inhibitor or ARB, especially by ARB. In conclusion, an ACE inhibitor and ARB prevent LV systolic and diastolic dysfunction as well as myocardial damage induced by excess beta-adrenergic stimulation.

Adrenergic beta-Agonists↗

PubMed2001

VEGF, basic-FGF, and TGF-beta in Crohn's disease and ulcerative colitis: a novel mechanism of chronic intestinal inflammation.

OBJECTIVE: Inflammatory bowel disease (IBD), the precise etiology of which remains unknown, is comprised of two forms of chronic intestinal inflammation; ulcerative colitis (UC) and Crohn's disease (CD). Recent evidence increasingly suggests that IBD is the result of dysfunctional immunoregulation manifested by inappropriate production of mucosal cytokines. An abnormal microcirculatory system has also been implicated in its pathogenesis. To elucidate the mechanism of ischemic change in IBD, we assesse serum concentration levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF), and plasma level of endothelin-1 (ET-1). We also investigated the expression of VEGF, b-FGF, and transforming growth factor-beta1,2,3 (TGF-beta1,2,3) in tissue by immunostaining. METHODS: Blood samples were obtained from 11 patients with UC, 11 patients with CD, and 10 patients as controls. Paraffin-embedded samples were used for an immunohistochemical study. RESULTS: The concentration levels (in picograms per milliliter) were as follows: for ET-1, UC: 127+/-47.0, CD: 167.3+/-35.1, and controls (asthma: 38.5+/-23.8, p < 0.01; diverticulitis: 40.5+/-25.6, p < 0.01), for b-FGF, UC: 9.2+/-1.9, CD: 9.1+/-1.5, and controls (asthma: 5.0+/-0, p < 0.01; diverticulitis: 5.0+/-0, p < 0.01), for VEGF, UC: 659.8+/-181.0, CD: 740.0+/-182.3, and controls (asthma: 193.7+/-58.7, p < 0.01; diverticulitis: 199.6+/-59.7, p < 0.01). The levels of VEGF and b-FGF were significantly higher in active IBD than those in the controls. There was a significant positive correlation among the serum levels of VEGF and b-FGF and the plasma level of ET-1; that is, elevated VEGF, b-FGF, and ET-1 levels correlated well with each other. Immunohistochemical studies showed increased venula in the submucosa and lamina propria. Overexpression of VEGF and b-FGF in endothelial cells was revealed and TGF-beta2 and TGF-beta3 were found in inflammatory cells of active IBD, but no change was observed around the vessels in the controls. CONCLUSIONS: It is suggested that the reciprocal reaction of these cytokines may contribute to angiogenesis in IBD b inducing intestinal ischemia through vasoconstriction.

Adult↗

PubMed2001

Systemic and mucosal immunizations with fibronectin-binding protein FBP54 induce protective immune responses against Streptococcus pyogenes challenge in mice.

The purpose of this study was to examine the suitability of fibronectin-binding protein FBP54 as a putative vaccine for Streptococcus pyogenes infections. When the distribution of the fbp54 gene among the clinical isolates representing various M serotypes was tested by PCR and Southern blot assays, it was found that all of the strains possess this gene. Furthermore, a significant increase in immunoglobulin G (IgG) antibody titers against FBP54 was observed in sera from patients with S. pyogenes infections compared with those from healthy volunteers (P < 0.005). Mice were immunized with FBP54 subcutaneously, orally, or nasally. An enzyme-linked immunosorbent assay revealed that antigen-specific IgG antibodies were induced in the sera of immunized mice, while high salivary levels of IgA antibodies were detected after oral and nasal immunizations. Mice subcutaneously or orally immunized with FBP54 survived significantly longer following the challenge with S. pyogenes than did nonimmunized mice (P < 0.001). These results indicate that FBP54 is a promising vaccine for the prevention of S. pyogenes infections.

Adhesins, Bacterial↗

PubMed2001

Coronary sinus occlusion enhances coronary collateral flow and reduces subendocardial ischemia.

On the hypothesis that coronary sinus occlusion (CSO) may reduce myocardial ischemia, we examined the effects of CSO on coronary collateral blood flow and on the distribution of regional myocardial blood flow (RMBF) in dogs. Thirty-eight anesthetized dogs underwent occlusion of the left anterior descending coronary artery with or without CSO and intact vasomotor tone. We measured RMBF and intramyocardial pressure (IMP) in the subendocardium (Endo) and subepicardium (Epi) separately. With intact vasomotor tone, CSO during ischemia significantly increased RMBF in the ischemic region (IR), particularly in Endo from 0.17 +/- 0.03 to 0.33 +/- 0.05 ml x min(-1) x g(-1) (P < 0.05), and increased the Endo/Epi from 0.59 +/- 0.10 to 1.15 +/- 0.15 (P < 0.01). These effects of CSO were partially abolished by adenosine. However, the Endo/Epi was still increased from 0.90 +/- 0.13 to 2.09 +/- 0.30 (P < 0.01). The changes in RMBF in IR were significantly correlated with the peak CS pressure during CSO. The Endo/Epi of IMP in IR was significantly decreased during CSO. In conclusion, CSO potentially enhances coronary collateral flow, and preserves the ischemic myocardium, especially in Endo.

Adenosine↗

PubMed2001

Flow-mediated release of nitric oxide in isolated, perfused rabbit lungs.

The effects of changing perfusate flow on lung nitric oxide (NO) production and pulmonary arterial pressure (Ppa) were tested during normoxia and hypoxia and after N(G)-monomethyl-L-arginine (L-NMMA) treatment during normoxia in both blood- and buffer-perfused rabbit lungs. Exhaled NO (eNO) was unaltered by changing perfusate flow in blood-perfused lungs. In buffer-perfused lungs, bolus injections of ACh into the pulmonary artery evoked a transient increase in eNO from 67 +/- 3 (SE) to 83 +/- 7 parts/billion with decrease in Ppa, whereas perfusate NO metabolites (pNOx) remained unchanged. Stepwise increments in flow from 25 to 150 ml/min caused corresponding stepwise elevations in eNO production (46 +/- 2 to 73 +/- 3 nl/min) without changes in pNOx during normoxia. Despite a reduction in the baseline level of eNO, flow-dependent increases in eNO were still observed during hypoxia. L-NMMA caused declines in both eNO and pNOx with a rise in Ppa. Pulmonary vascular conductance progressively increased with increasing flow during normoxia and hypoxia. However, L-NMMA blocked the flow-dependent increase in conductance over the range of 50-150 ml/min of flow. In the more physiological conditions of blood perfusion, eNO does not reflect endothelial NO production. However, from the buffer perfusion study, we suggest that endothelial NO production secondary to increasing flow, may contribute to capillary recruitment and/or shear stress-induced vasodilation.

Acetylcholine↗

PubMed2001

Role of airway nitric oxide on the regulation of pulmonary circulation by carbon dioxide.

The effects of hypercapnia (CO(2)) confined to either the alveolar space or the intravascular perfusate on exhaled nitric oxide (NO), perfusate NO metabolites (NOx), and pulmonary arterial pressure (Ppa) were examined during normoxia and progressive 20-min hypoxia in isolated blood- and buffer-perfused rabbit lungs. In blood-perfused lungs, when alveolar CO(2) concentration was increased from 0 to 12%, exhaled NO decreased, whereas Ppa increased. Increments of intravascular CO(2) levels increased Ppa without changes in exhaled NO. In buffer-perfused lungs, alveolar CO(2) increased Ppa with reductions in both exhaled NO from 93.8 to 61.7 (SE) nl/min (P < 0.01) and perfusate NOx from 4.8 to 1.8 nmol/min (P < 0.01). In contrast, intravascular CO(2) did not affect either exhaled NO or Ppa despite a tendency for perfusate NOx to decline. Progressive hypoxia elevated Ppa by 28% from baseline with a reduction in exhaled NO during normocapnia. Alveolar hypercapnia enhanced hypoxic Ppa response up to 50% with a further decline in exhaled NO. Hypercapnia did not alter the apparent K(m) for O(2), whereas it significantly decreased the V(max) from 66.7 to 55.6 nl/min. These results suggest that alveolar CO(2) inhibits epithelial NO synthase activity noncompetitively and that the suppressed NO production by hypercapnia augments hypoxic pulmonary vasoconstriction, resulting in improved ventilation-perfusion matching.

Animals↗