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Biomedical subjects

K Kuno

Publications and source records attributed to K Kuno.

At least 109 records · Page 6Linked to original sources
PubMed1994

Cloning of a cDNA encoding a mouse homolog of the interleukin-8 receptor.

A mouse cDNA library was screened using a DNA fragment generated by polymerase chain reaction (PCR) with oligodeoxyribonucleotide primers which were derived from the conserved sequences in cDNAs encoding the human and rabbit interleukin-8 receptors (hIL-8R and rIL-8R). A novel cDNA was obtained encoding 359 amino acids (aa) with seven putative transmembrane portions similar to hIL-8R and rIL-8R. Its aa sequence shows 64 and 69% homology to those of type-1 and type-2 hIL-8R, respectively. COS-7 cells transfected with the isolated cDNA in a mammalian expression vector bind IL-8, but do not bind a related protein, monocyte chemotactic and activating factor, suggesting that the isolated cDNA encodes the mouse homolog of IL-8R. Northern blot analysis showed that mRNA of this clone was highly expressed in mouse peritoneal neutrophils, and the single band was observed in Southern blotting analysis on mouse genomic DNA digested with HindIII or KpnI, suggesting that this is a single-copy gene.

Amino Acid Sequence↗
PubMed1994

The IL-1 receptor signaling pathway.

Interleukin-1 (IL-1) exerts pleiotropic effects on a variety of tissues through binding to its receptor. Two distinct types of receptors for IL-1 have been characterized in mouse and human. Most of the IL-1 signal has been shown to be transmitted through type I IL-1R (80 kDa) in T lymphocytes as well as B lymphocytes and monocytes. Type II receptor may act as a suppressor of IL-1 biological activities by competing in binding with type I receptors on the cell surface. Functional studies of the type I IL-1R demonstrated that the cytoplasmic segments, possessing a sequence similarity with the Drosophila Toll gene product or IL-6R beta chain, gp130, are important for transmitting activity that induces cytokine genes. In the past three years, several groups reported that IL-1 and tumor necrosis factor (TNF) rapidly induce sphingomyelin turnover in various types of cells, producing ceramide, which may act as a second messenger molecule in an intracellular signaling cascade. Activation of both acid and neutral sphingomyelinases (SMases) has been suggested, and Schutz et al. proposed that the phosphatidylcholine-phospholipase C/acid SMase pathway is involved in TNF-induced NF-kappa B activation. However, our recent study showed that the NF-kappa B activation is induced by IL-1/TNF in fibroblasts from patients with type A Niemann-Pick disease, with acid SMase deficiency. This finding implies that acid SMase activity is not essential for the activation of NF-kappa B by IL-1/TNF at least in fibroblasts. Other signaling pathways including neutral SMase and unidentified protein kinases may be important for NF-kappa B-mediated cytokine gene activation.

Amino Acid Sequence↗
PubMed1994

Carcinoma of the colon in children: case report and review of the Japanese literature.

A 15-year-old female presenting with anemia and positive for occult blood was diagnosed as having an adenomatous polyp with mild atypia in the cecum by colonoscopy. Microscopically, the majority of the surface of the tubulovillous adenoma was occupied by a well-differentiated adenocarcinoma, indicating that the adenoma-carcinoma sequence is involved in the development of colon cancers, even in children. Forty-three cases of proven carcinoma of the colon in Japanese children aged under 15 years are also reviewed. The majority of the patients were aged over 10. Although an emergency laparotomy was undertaken in 42.5% of these patients, the signs and symptoms observed in these children did not markedly differ from those of adults. Colon cancer should not be excluded in children only on the basis of age, and barium enema and colonoscopy should therefore be applied to pediatric patients with unexplainable bleeding and abdominal pain, especially those over 10 years of age.

Adenocarcinoma↗
PubMed1994

Detection of tumor necrosis factor-alpha, interleukin-6, and fetal fibronectin in the lower genital tract during pregnancy: relation to outcome.

OBJECTIVE: Our purpose was to determine whether tumor necrosis factor-alpha, interleukin-6, and fetal fibronectin could be identified in the lower genital tract during pregnancy and whether their occurrence was associated with preterm delivery. STUDY DESIGN: A prospective cohort study was undertaken of 111 pregnant women in which cervicovaginal swabs were obtained at < 37 weeks' gestation. Seventy-three specimens were obtained from women during routine prenatal examination, whereas 38 specimens were obtained from women undergoing evaluation of preterm labor. Interleukin-6 and fetal fibronectin levels were determined by enzyme-linked immunosorbent assays, whereas tumor necrosis factor-alpha determinations were by bioassay. Urinary tract and lower genital tract samples were cultured for evidence of infection. The rates of maternal and neonatal complications were assessed. RESULTS: In patients undergoing evaluation for preterm labor the presence of tumor necrosis factor-alpha or fetal fibronectin was associated with an increased prevalence of preterm delivery. Women with tumor necrosis factor-alpha had a 6.19 greater risk (p < 0.005), whereas the presence of fetal fibronectin was associated with a 4.81 greater risk (p < 0.05), of preterm birth. This association was not evident in women who were sampled during routine prenatal examinations. In all women the presence of cytokines in the lower genital tract correlated with detection of fetal fibronectin. CONCLUSION: Localized inflammatory responses may lead to microscopic disruption in the amniotic membranes, leading to leakage of fibronectin. In patients being evaluated for preterm labor, the presence of tumor necrosis factor-alpha or fetal fibronectin in the lower genital tract is predictive of subsequent preterm delivery.

Adolescent↗
PubMed1994

Acid sphingomyelinase is not essential for the IL-1 and tumor necrosis factor receptor signaling pathway leading to NFkB activation.

A recent report has suggested that tumor necrosis factor (TNF) utilizes acid sphingomyelinase (SMase) pathway to activate NFkB (Schutze et al. 1992. Cell 71:765). To directly investigate the role of acid SMase in IL-1 and TNF receptor-mediated signal transduction, we examined the ability of Niemann-Pick disease (NPD) type A fibroblasts, which are deficient in acid SMase, to induce IL-8 gene expression through activating NFkB. Unexpectedly, IL-1 alpha and TNF-alpha efficiently induced IL-8 production and IL-8 mRNA in NPD type A fibroblasts as in normal fibroblasts. Furthermore, activation of NFkB was also induced in NPD type A fibroblasts in response to IL-1 alpha and TNF-alpha stimulation to a similar extent as in normal fibroblasts. These results provide evidence that acid SMase is not essential in IL-1 and TNF receptor signaling leading to NFkB activation as well as the cytokine gene activation which is regulated by NFkB.

Base Sequence↗
PubMed1994

Enhancement human cytomegalovirus replication in a human lung fibroblast cell line by interleukin-8.

We examined the effects of interleukin-8 (IL-8) on cytomegalovirus (CMV) replication in human fibroblasts. Exposure of fibroblasts to IL-8 augmented both infectious virus production and replication of CMV, with concomitant increases in the levels of both the transcript of the CMV pp71 genome and the synthesis of the CMV late antigen. We also found that CMV selectively induced transcripts of the IL-8 type 1 receptor in fibroblasts. These results suggest that IL-8 also contributes to inflammatory diseases by enhancing CMV replication and that CMV regulates its production through induction of IL-8 receptor.

Cell Line↗
PubMed1994

Oxygen desaturation following voluntary hyperventilation in normal subjects.

To investigate the severity of oxygen desaturation following voluntary hyperventilation (VHV) in normal subjects and its possible relation to chemoresponsiveness, we examined respiration following VHV in 16 normal male subjects. Monitoring was performed according to the standard polysomnography protocol including measurements of arterial oxygen saturation (SaO2) and transcutaneous PCO2 (PtcCO2). The subjects hyperventilated voluntarily for 3 min, and were then observed for more than 15 min. They hyperventilated again for another 3 min, and were followed again for more than 15 min. Eleven subjects fell into non-REM sleep after VHV, and their mean lowest SaO2 was 67.6 +/- 13.0% (n = 15 trials in 11 subjects, mean +/- SD). Falling asleep during hypocapnia caused desaturation, and periodic breathing was invariably observed soon after. The difference between the PtcCO2 during non-REM sleep with stable breathing and the PtcCO2 when the SaO2 was 90% following VHV was defined as the delta PtcCO2 (90). The delta PtcCO2 (90) and hypoxic ventilatory response (HVR) were positively and significantly correlated (r = 0.73, p < 0.01). While the subjects were awake, the mean lowest SaO2 was 73.5 +/- 17.4% (17 trials in 12 subjects). Remaining awake induced oxygen desaturation in some subjects but not in others. In one subject, desaturation during the waking state was caused by hypoventilation, not by central apnea. In the seven subjects whose respiration following VHV was monitored during the waking state in one trial and during the sleeping state in another trial, plots of the PtcCO2-SaO2 relationship for the waking state were generally positioned above those made for the sleeping state.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Pneumonitis associated with natural and recombinant interferon alfa therapy for chronic hepatitis C.

We report three cases of chronic hepatitis C (HC) with pneumonitis, suspected to be caused by natural and recombinant interferon (INF) alfa treatments. The patients were administered INF through intramuscular injection. All three patients developed acute respiratory failure (PaO2 < or = 60 mm Hg) with bilateral lung infiltration. One of the patient's condition improved after the cessation of INF treatment, without any other therapy. The other two patients were administered corticosteroids, and one patient's condition improved, while in the other patient the pneumonitis persisted, even after a high dose of corticosteroids. To our knowledge, these three cases are the first report of pneumonitis associated with INF alfa in patients with chronic HC.

Aged↗
PubMed1994

An automated method to assess the distribution of low attenuation areas on chest CT scans in chronic pulmonary emphysema patients.

We developed an automated method to recognize the lung in a computed tomographic (CT) image. With computer-assisted analysis, we were able to describe the continuous low attenuation (less than -960 Hounsfield units) areas (CLA) on chest CT scans. The size (CLAs) and number (CLAn) of the CLA and the percentage of total lung area occupied by low attenuation area (LAA%) were measured using CT scans obtained from 24 patients with chronic pulmonary emphysema (CPE) and 13 control patients. The automated algorithm recognized the lung areas successfully in all patients. The CLAs and LAA% were significantly higher, and CLAn was significantly lower in patients with CPE than in controls. There was a significant correlation between CT parameters and pulmonary function test results. The histograms of the size of CLA could be represented as a power function in each patient. This automated method should be useful in objectively defining the affected areas in the lungs of patients with CPE.

Aged↗
PubMed1994

[The prognostic value of brain CT scan in infants with periventricular leukomalacia].

Brain CT scan was performed at 40 weeks of conceptional age in 17 preterm infants with periventricular leukomalacia (PVL). The finding of periventricular low density was not useful in differentiating patients with PVL from normal infants, because this finding was seen in 40% of normal infants. The following findings were characteristic of PVL: (1) a marked low density area in centrum semiovale, (2) an irregular outline of ventricular wall, and (3) low density spots in periventricular white matter. The findings of ventricular dilation with irregular wall and marked low density area in centrum semiovale were correlated with a finding of volume loss on MRI during late infancy and the severity of neurological impairment, especially in severely affected patients. Marked low density area in centrum semiovale was characteristic of severe PVL demonstrated on brain CT scan.

Brain↗
PubMed1994

[Pharmacokinetic and clinical studies of cefozopran in the field of pediatrics].

Pharmacokinetic and clinical studies on cefozopran (CZOP, SCE-2787), a new cephalosporin antibiotic, were carried out in the field of pediatrics. The results obtained are summarized below. 1. Serum concentrations and urinary excretion rates were determined after intravenous bolus injection of CZOP at a dose of 20 mg/kg for 5 minutes in 3 cases. The mean serum concentration of CZOP was 45.9 micrograms/ml at 30 minutes with the serum half-life of 1.77 hours. The mean cumulative urinary excretion rate in the first 8 hours after administration was 71.4%. 2. Fourteen patients with bacterial infections (pneumonia 9 cases, urinary tract infection 4 cases and lymphadenitis 1 case) were treated with CZOP at a daily dose of 55.8-65.7 mg/kg. The overall clinical efficacy and bacteriological eradication rates were both 100%. 3. No adverse reactions were observed. Abnormal laboratory test results were mild, slight elevation of GOT and GOT, GPT & LDH in 1 each and eosinophilia and thrombocytosis in 2 cases each.

Cephalosporins↗
PubMed1994

[Laboratory and clinical studies on biapenem (L-627) in the field of pediatrics].

Laboratory and clinical studies on biapenem (L-627), a new carbapenem antibiotic, were carried out in the field of pediatrics. 1. Antibacterial activities of L-627 against clinically isolated organisms in our department were generally high. 2. After 30 minutes intravenous infusion of L-627 at a dose of 10 mg/kg in 3 and of 12 mg/kg in 2 children, peak plasma levels of L-627 ranged from 25.6 to 44.6 micrograms/ml at the end of the infusion. The half-lives were from 0.68 to 0.94 hours. The cumulative urinary recovery rates in the first 6 hours after the start of drip infusion ranged from 11.4 to 47.5%. 3. 14 patients with various bacterial infections were treated with L-627. The clinical efficacy rate was also 92.9% and the bacteriological efficacy rate was also 92.9%. 4. No side effects were observed. A few abnormal laboratory test results were obtained, but they were mild with slight elevation of GOT/GPT and platelets in 1 each.

Bacteria↗
PubMed1994

[The prognostic value of neonatal cranial ultrasonography in infants with periventricular leukomalacia].

Serial cranial ultrasonography was performed in 17 preterm infants with periventricular leukomalacia (PVL) in the neonatal period. Periventricular high-echogenicities were observed in all infants, and periventricular cysts in 14/17 infants (82%). We investigated the correlation between these findings and abnormalities on MRI in late infancy. Periventricular high-echogenicity was correlated with the extent of periventricular high-intensities on T2-weighted images of late infantile MRI. The extent of periventricular cysts was correlated with that of volume loss on MRI during late infancy. The degree of periventricular echo-lesion was associated with that of neurological abnormalities of infants. The extent of periventricular echo-lesion has the same prognostic value as findings on MRI in infants with PVL.

Cerebral Ventricles↗
PubMed1994

[Treatment of unresectable non-small cell lung cancer (NSCLC) with carboplatin and chronic daily administration of oral etoposide].

CBDCA has only modest activity against NSCLC, but it is less toxic than cisplatin (CDDP). And CB DCA has a proven synergistic effect with etoposide. On the other hand, etoposide is schedule dependent and when give daily peros has activity against several tumors. So we conducted a trial to evaluate the efficacy of a combination of CBDCA and chronic daily administration of oral etoposide for previously untreated unresectable NSCLC. The treatment schedule consisted of CBDCA 400 mg/m2 on day 1 and chronic daily administration of oral etoposide of 50 mg/day/body for 21 consecutive days every 28 days. Twenty-nine of 36 enrolled patients were eligible. The response rate was 27.6% (95% confidence interval: 11.1-43.9%). The median survival time was 405 days. The primary toxicity was myelosuppression: leukopenia, neutropenia, anemia and thrombocytopenia of Grade 3 or 4 were 14.7%, 29.4%, 26.5%, and 5.9%, respectively. No bleeding episodes or toxic death were observed. Nonhematologic toxicity was slight, and there was no severe gastrointestinal toxicity. This combination was effective against NSCLC with tolerable toxicity and an "easily tolerated outpatient regimen".

Adenocarcinoma↗
PubMed1993

Structure and function of the intracellular portion of the mouse interleukin 1 receptor (type I). Determining the essential region for transducing signals to activate the interleukin 8 gene.

The structural and functional relationships of the intracellular portion of mouse interleukin 1 receptor (muIL-1R) type I were examined with regard to activation of the human IL-8 gene in the Jurkat T cell line. C-terminal deletion mutations of muIL-1R revealed that the C-terminal boundary for receptor function is localized between 28 and 42 amino acids from the C-terminal end. The internal deletion mutants between amino acids 364 and 474 had a loss of activity, demonstrating the requirement for a large region of the mIL-1R cytoplasmic portion for receptor function. Amino acid substitution revealed that the putative nuclear localization elements (amino acids at 429-433, 523-527, and 507-519) and putative protein kinase C or A acceptor sites (Ser-431, Ser-509, Ser-528) do not participate in IL-1 signaling to induce IL-8 gene expression. A truncated mutation within the segment, which possesses homology with gp130, beta chain of IL-6R, or a point mutation of box 1- and box 2-like elements within the gp130 homologous segment, abolished the capacity to induce IL-8 gene expression, suggesting similar structural requirements in the cytoplasmic portion of several cytokine receptors.

Amino Acid Sequence↗