Search PubMed⌕ Search

Biomedical subjects

K Kuno

Publications and source records attributed to K Kuno.

At least 91 records · Page 5Linked to original sources

[Outcome of long-term nasal intermittent positive pressure ventilation in 41 patients with hypercapnic respiratory failure].

Nasal intermittent positive pressure ventilation (NIPPV) is widely used in domiciliary treatment of chronic ventilatory disorders. The outcomes of long-term NIPPV were analyzed in 41 patients with hypercapnic respiratory failure due to pulmonary tuberculosis sequelae (PTS; n = 17), neuromuscular disease (NMD; n = 8), kyphoscoliosis (KS; n = 7), chronic obstructive pulmonary disease (COPD; n = 6), and miscellaneous diseases (n = 3). Twenty-seven patients with chronic conditions but without acute exacerbations began receiving NIPPV, and fourteen patients began receiving NIPPV after an acute exacerbation. Outcome measures included the probability of continuing NIPPV, survival after starting NIPPV, survival after starting home oxygen therapy (HOT), arterial blood gases, nocturnal oxygen saturation, pulmonary function, and the number of hospital days. Two patients with PTS died, 7 and 40 months after starting NIPPV. Two patients (one with PTS and one with COPD) switched from NIPPV to intermittent positive pressure ventilation via a tracheostomy. The condition of one patient with NMD improved and NIPPV was discontinued. The three-year and five-year probabilities of continuing NIPPV in all patients were 82%, and 71%, respectively. The survival rates three and five years after starting NIPPV were 97% and 85%, respectively. The survival rates one to nine years, and ten to eleven years after starting HOT were 98% and 65%, respectively. The arterial PO2 and PCO2, nocturnal oxygen saturation, vital capacity, and forced expiratory volume, in one second all improved after NIPPV was begun. NIPPV also reduced the number of hospital days, particularly in patients with KS. In conclusion, the long-term outcome of NIPPV in patients with hypercapnic respiratory failure is encouraging.

Adult↗

[Temporary use of chest negative pressure ventilation to facilitate closure of a tracheal stoma before domiciliary nasal intermittent positive pressure ventilation].

A 67-year-old patient with pulmonary tuberculosis sequela had undergone a tracheostomy. The patient was receiving nasal intermittent positive pressure ventilation and the stoma failed to close. Temporary use of chest negative pressure ventilation facilitated closure of the stoma and probably shortened the patient's hospital stay. Nasal intermittent positive pressure ventilation at home was begun safely and effectively.

Aged↗

[Pharmacokinetic and clinical evaluation of azithromycin in pediatrics].

Azithromycin (AZM), a new macrolide antibiotic, in fine granules and in capsules was administered at a standard dose of 10 mg/kg once daily for 3 days to pediatric patients with bacterial infections. AZM was studied for its pharmacokinetic and clinical evaluation. 1. AZM possessed potent activity against Gram-positive bacteria and Gram-negative bacteria that had been clinically isolated. 2. Plasma samples were collected from two patients diagnosed as having pneumonia or enteritis, and urine samples were collected from one patient diagnosed as having pneumonia for drug level determination. The drug concentrations in plasma were 0.095 and 0.204 microgram/ml just before the end of treatment, and 0.017 and 0.096 microgram/ml at 48 hours post-treatment. The drug concentrations in urine were 5.16 micrograms/ml and 5.63 micrograms/ml during a period between 24 and 48 hours and between 48 and 72 hours after the start of treatment, respectively. 3. The drug was found effective in 37 of 38 cases with various pediatric infections. AZM treatment eradicated bacteria in 17 of 30 strains (56.7%). 4. One patient complained of mild vomiting, while abnormal laboratory test results indicating mild eosinophilia were reported in four cases.

Anti-Bacterial Agents↗

Identification of an I kappa B alpha-associated protein kinase in a human monocytic cell line and determination of its phosphorylation sites on I kappa B alpha.

Nuclear factor kappa B (NF-kappa B) is stored in the cytoplasm as an inactive form through interaction with I kappa B. Stimulation of cells leads to a rapid phosphorylation of I kappa B alpha, which is presumed to be important for the subsequent degradation. We have recently reported the establishment of a lipopolysaccharide (LPS)-dependent cell-free activation system of NF-kappa B in association with the induction of I kappa B alpha phosphorylation. In this study, we have identified a kinase in cell extracts from the LPS-stimulated human monocytic cell line, THP-1, that specifically binds and phosphorylates I kappa B alpha. LPS stimulation transiently enhanced the I kappa B alpha-bound kinase activity in THP-1 cells. Mutational analyses of I kappa B alpha and competition experiments with the synthetic peptides identified major phosphorylation sites by the bound kinase as Ser and Thr residues in the C-terminal acidic domain of I kappa B alpha. Moreover, we show that the peptide, corresponding to the C-terminal acidic domain of I kappa B alpha, blocked the LPS-induced NF-kappa B activation as well as inducible phosphorylation of endogenous I kappa B alpha in a cell-free system using THP-1 cells. These results suggested that the bound kinase is involved in the signaling pathway of LPS by inducing the phosphorylation of the C-terminal region of I kappa B alpha and subsequent dissociation of the NF-kappa B.I kappa B alpha complex.

Amino Acid Sequence↗

Establishment of lipopolysaccharide-dependent nuclear factor kappa B activation in a cell-free system.

Nuclear factor kappa B (NF-kappa B), consisting of p50 and p65, is bound to a cytoplasmic retention protein, I kappa B, in a resting state, and the stimulation of cells with a variety of inflammatory stimuli induces the dissociation of NF-kappa B from I kappa B and the nuclear translocation of NF-kappa B, thereby activating several genes involved in inflammatory responses, such as interleukin (IL)-6, IL-8, and tumor necrosis factor alpha. In order to elucidate the precise mechanism of NF-kappa B activation, we have established lipopolysaccharide (LPS)-dependent NF-kappa B activation in a cell-free system using plasma membrane-enriched, cytosol, and nuclear fractions extracted from a human monocytic cell line, THP-1, by disruption with sonication followed by a differential centrifugation. The combination of plasma membrane-enriched fraction and cytosol was sufficient to activate NF-kappa B in a LPS/CD14-dependent manner only in the presence of ATP as judged by the binding of NF-kappa B to the IL-8 gene kappa B site on an electrophoretic mobility shift assay. LPS-dependent NF-kappa B activation was inhibited by protein kinase inhibitors, such as staurosporine, herbimycin A, tyrphostin, and genistein, but not mitogen-activated protein kinase substrate, cGMP-dependent protein kinase, cAMP-dependent protein kinase, protein kinase C, and calmodulin-dependent protein kinase II inhibitory peptides, suggesting that staurosporine-sensitive kinase(s) as well as tyrosine kinase(s) are involved in LPS-mediated NF-kappa B activation. In addition, LPS induced the phosphorylation of I kappa B-alpha, starting at 5 min after the stimulation in a cell-free system. Moreover, the phosphorylation was inhibited by herbimycin A and tyrphostin, but not staurosporine, suggesting that these protein kinase inhibitors act at distinct steps of signal transmission. Establishment of ligand-dependent activation of NF-kappa B in a cell-free system will facilitate identification of protein kinase(s) and its substrate(s) involved in LPS-mediated NF-kappa B activation.

Amino Acid Sequence↗

Molecular analysis of the cytokine network involved in cachexia in colon 26 adenocarcinoma-bearing mice.

Two clones, one cachexigenic (clone 20) and the other noncachexigenic (clone 5), from a murine colon adenocarcinoma, colon 26 cells, were used to analyze the involvement of immune reactions as well as the cytokine network in cachexia. Clone 20 induced cachexia in nude and SCID mice as well as in normal BALB/c mice, suggesting that lymphocytes played little, if any, role in the process. Both clones failed to express mRNA of interleukin (IL) 1 alpha, IL-1 beta, IL-6, and tumor necrosis factor alpha in vitro with or without the coculture of NIH3T3 cells or spleen cells. However, IL-6 mRNA was selectively detected at the tumor site of clone 20 but not at that of clone 5-bearing mice. In contrast, tumor necrosis factor alpha mRNA was detected at tumor sites and in spleens of only clone 5-bearing mice, suggesting a potential role of IL-6, but not tumor necrosis factor alpha, in inducing cachexia. Anti-IL-6 antibody partially reversed the weight loss induced by clone 20, whereas the continuous infusion of IL-6 failed to cause weight loss, despite being associated with an elevation of a serum acute phase protein. These results suggest that IL-6 is necessary but not sufficient for the induction of cachexia. Both clones expressed IL-6 mRNA in the presence of IL-1 in vitro, and mice bearing either clone expressed IL-1 beta mRNA at the tumor site. Moreover, IL-1 receptor antagonist (IL-1Ra) mRNA was detected at the tumor site of clone 5-bearing mice but not at that of clone 20-bearing mice, suggesting that IL-1Ra might block IL-1 activity to reduce IL-6 production in clone 5-bearing mice. However, the transfection of clone 20 with IL-1Ra cDNA failed to abolish its capacity to produce IL-6 and to cause cachexia. Collectively, additional factor(s) besides IL-1Ra and IL-1 beta may control IL-6 and some other cachexigenic factor production, thereby causing cachexia in this model.

Adenocarcinoma↗

Expression of both types of human interleukin-8 receptors on mature neutrophils, monocytes, and natural killer cells.

cDNA cloning revealed the presence of two related but distinct types of human interleukin-8 (IL-8) receptors, type I (type A) and type II (type B). By immunizing rabbits with glutathione-S-transferase fused with the NH2-terminal domain of each type of IL-8 receptor, we prepared polyclonal antibodies that specifically recognized the NH2-terminal domain of each type of IL-8 receptor. Immunofluorescence analysis of human peripheral blood leukocytes demonstrated that mature granulocytes except eosinophils express both types of IL-8 receptors. A majority of monocytes and CD16+ natural killer (NK) cells in peripheral blood were stained with both antibodies, whereas CD3+ T or CD20+ B lymphocytes in peripheral blood or CD34+ cells in cord blood were not stained with either antibody. These results suggest that both types of human IL-8 receptors were coordinately and selectively expressed in mature granulocytes, monocytes, and CD16+ NK cells.

Amino Acid Sequence↗

Preparation of specific antibodies against murine IL-1ra and the establishment of IL-1ra as an endogenous regulator of bacteria-induced fulminant hepatitis in mice.

Blocking monoclonal antibodies (mAbs) specific to mouse interleukin-1 receptor antagonist (IL-1ra) were prepared by immunizing Armenian hamsters with recombinant mouse IL-1ra. A sensitive and specific ELISA against mouse IL-1ra was also established. In Propionibacterium acnes-induced liver injury, P. acnes induced transient increase of serum tumor necrosis factor-alpha levels but not those of IL-1ra, IL-1, and IL-6. However, subsequent lipopolysaccharide (LPS) challenge induced the increase of serum levels of all these cytokines and the peak serum IL-1ra level was more than 20 times as high as serum IL-1 levels. Immunohistochemical analysis demonstrated that IL-1ra was predominantly produced by hepatocytes during the course of the priming phase by P. acnes and eliciting phase by LPS challenge. Furthermore, the administration of a mAb to mouse IL-1ra exacerbates the liver injury induced by P. acnes and sublethal dose of LPS, suggesting a protective role of endogenous IL-1ra in this liver injury model.

Animals↗

New design of N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) lung imaging in the patient with lung cancer.

N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) was injected intravenously into primary non small cell lung carcinoma patients (n = 17). The average pixel count ratios of the cancerous area to the whole lung was measured in the initial and delayed images. In the initial image, this ratio was less than 1.0 for the entire group of patients, and was thought to reflect decreased blood flow in the cancerous tissues. The rate of counts within a ROI in the delayed image to counts in the same ROI in the initial image was also calculated and called the remain rate. The remain rate (delayed count/initial count) was significantly higher in the cancerous area than in the whole lung (0.65 +/- 0.30, median 0.62, 0.38 +/- 0.05, median 0.38, p < 0.01). This observation was thought to be due to a relative decrease in the blood flow and the accumulation of IMP, which forms pools within the alveolar spaces of the cancerous areas. The image prepared with the remain rate revealed a hot image in the cancerous regions, even when this was not apparent in the delayed image. The remain rate image may therefore be useful in the identification of cancerous areas in lung tissue if it is used in comparison with the initial image.

Adult↗

Age-related changes in the static and dynamic mechanical properties of mouse lungs.

To investigate the effects of aging on pulmonary mechanical properties in mice, we devised a new experimental apparatus to measure the respiratory impedance of excised lungs in mice and examined age-related changes in both static and dynamic properties. In an accelerated senescence-resistant strain of mice, SAMR1 (Takeda, T., Y. Fukuchi, Y. Uejima, K. Teramoto, T. Oka and H. Orino, J. Am. Geriatr. Soc. 39: 911-919, 1991), ranging from 3 to 24 months of age, static compliance (Cst) as well as total lung capacity increased significantly with age, whereas specific compliance and the K value, as determined by exponential analysis, showed no significant change. In the dynamic study, dynamic compliance (Cdyn) increased significantly with age, whereas the frequency dependence of Cdyn (Cdyn/Cst) did not vary with age. From these results we concluded that lung elasticity, normalized to lung volume, remained constant with age and that the effects of aging on pulmonary mechanics might be solely derived from increases in lung volume in the SAMR1 strain of mice.

Age Factors↗

Clinical, neurophysiologic, and neuropathological features of an infant with brain damage of total asphyxia type (Myers).

An infant who demonstrated clinical features compatible with total asphyxia is reported. Immediately after birth, the patient manifested severe hypotonia and total absence of cranial nerve functions. Magnetic resonance imaging revealed abnormal intensity of the thalamus and putamen, and atrophy of the brainstem. Late components of brainstem auditory evoked potential were absent, but electroencephalography was normal. Postmortem autopsy revealed destructive lesions of the brainstem tegmentum, thalamus, basal ganglia, and spinal cord, but preserved cerebral cortex; findings consistent with those of total asphyxia as reported by Myers, and attributable to prenatal insult.

Asphyxia Neonatorum↗

Human MCAF gene transfer enhances the metastatic capacity of a mouse cachectic adenocarcinoma cell line in vivo.

PURPOSE: To evaluate the effect of monocyte chemotactic and activating factor (MCAF/MCP-1/JE) on tumor progression and metastasis. METHODS: Cachexia-inducing adenocarcinoma cells (cell line colon 26, clone 20) were transfected with either a control plasmid or MCAF expression vector. Spontaneous lung metastases were determined in mouse. RESULTS: The production of MCAF reached 0.4 ng/ml in vitro when transfectant cells were cultured at a cell density of 5 x 10(4) cells/ml for 3 days. Transfection of MCAF expression vector did not affect the growth rate in vitro. Also, after MCAF-transfection, the size of tumors after intra-footpad inoculation was similar to that of the parental cells. When the primary tumors were resected on the 10th day after inoculation, the incidence of spontaneous lung metastasis was less than 20% in both cells. The number of endothelial cells in the primary tumor rapidly increased from the 10th to the 14th day after inoculation, as revealed by immunohistochemical staining. In accordance with enhanced angiogenesis, the incidence rates of spontaneous metastasis increased when the primary tumors were resected on the 14th day after inoculation. Moreover, the spontaneous lung metastases were augmented in the animals injected with MCAF-transfectants compared to those injected with parental cells with a concomitant increase of angiogenesis. CONCLUSIONS: These results suggest that MCAF may augment the metastastic potential by modulating tumor associated angiogenesis.

Adenocarcinoma↗

Effect of carbon dioxide on facial nerve blood flow in rabbits.

We investigated blood flow to the facial nerve, cerebral cortex, brain stem, and dura mater in 16 white rabbits using a nonradioactive microsphere technique at various levels of arterial carbon dioxide tension. The blood flow to the facial nerve in the 32 temporal bones was 59.1 +/- 32.9 microliters/g/min. Unlike cerebral blood flow, blood flow to the facial nerve and dura mater did not show any marked increase upon carbon dioxide inhalation.

Administration, Inhalation↗

[Clinical studies on SY5555 in the field of pediatrics].

Clinical studies on SY5555 dry syrup, a new oral penem antibiotic, were carried out in the field of pediatrics. The following results were obtained. 1. SY5555 was administered to 10 children with various bacterial infections (2 patients with acute tonsillitis, 2 with acute bronchitis, 1 with pharyngitis, 2 with scarlet fever, 1 with pertussis and 2 with urinary tract infections). The overall clinical efficacy rate was 90%. 2. Side effects or abnormal laboratory test values were not observed except for loose stool in 1 and eosinophilia in 1.

Administration, Oral↗