Search PubMed⌕ Search

Biomedical subjects

K Kuno

Publications and source records attributed to K Kuno.

At least 127 records · Page 7Linked to original sources

N-isopropyl-p-iodoamphetamine receptors in normal and cancerous tissue of the human lung.

N-Isopropyl-p-iodoamphetamine (IMP) receptors in normal human lung tissue were characterized using a radioligand binding assay with iodine-125 IMP as the ligand. Saturation binding studies revealed the presence of two binding sites with dissociation constant (Kd) values of 53 +/- 2 and 4687 +/- 124 nM and maximum binding capacity (Bmax) values of 7 +/- 1 and 133 +/- 27 pmol/mg protein (n = 5) respectively. The IC50 values of various amines were as follows: IMP, 9 x 10(-5) M; propranolol, 5 x 10(-4) M; haloperidol, 6 x 10(-4) M; ketamine, 9 x 10(-3) M; dopamine, 1 x 10(-2) M. The IMP receptors of cancerous tissue obtained from human lung also had two binding sites with Kd values of 54 +/- 2 and 5277 +/- 652 nM and Bmax values of 7 +/- 1 and 103 +/- 21 pmol/mg protein (n = 3) respectively. There was no significant difference in binding parameters between normal and cancerous lung tissue. These results demonstrate the existence of IMP receptors and suggest that cancer does not affect the nature of IMP receptors in human lung tissue.

Adult↗

Expression of recombinant rabbit IL-8 in Escherichia coli and establishment of the essential involvement of IL-8 in recruiting neutrophils into lipopolysaccharide-induced inflammatory site of rabbit skin.

In order to establish the pathophysiological roles of IL-8, rabbit IL-8 was expressed in Escherichia coli and purified to homogeneity by sequential chromatography on heparin agarose, CM-HPLC, and RP-HPLC. The purified recombinant rabbit IL-8 was homogeneous on SDS-PAGE and the ED50 of neutrophil chemotactic activity for rabbit peritoneal neutrophils was 2 ng/ml. The binding of 125I-labeled rabbit IL-8 to rabbit neutrophils was inhibited by unlabeled human IL-8 as well as rabbit IL-8 but not by another leucocyte chemotactic cytokine (chemokine), monocyte chemotactic and activating factor. Scatchard plot analysis of the binding of 125I-labeled rabbit IL-8 to rabbit peritoneal neutrophils revealed that the rabbit neutrophils have two affinity classes of receptors for IL-8 (Kd = 2.3 nM, 4.1 x 10(4) sites/cell; Kd = 18.0 nM, 11.4 x 10(4) sites/cell). It was found that a previously generated mouse anti-human IL-8 mAb, WS-4, inhibited the binding of 125I-labeled rabbit IL-8 to rabbit neutrophils, and blocked neutrophil chemotaxis in vitro in a specific and dose-dependent manner. An ELISA system for rabbit IL-8 was established using this mAb and guinea pig polyclonal antibodies to recombinant rabbit IL-8 to measure the levels of IL-8 in rabbit plasma. Intravenous administration of lipopolysaccharide (LPS) (100 micrograms) in rabbits caused the highest level of IL-8 in blood at around 2 h. Intravenous administration of WS-4 (10 mg) inhibited neutrophil infiltration at the site of LPS injection into the rabbit skin, suggesting that IL-8 is essential in the recruitment of neutrophils at sites of acute inflammation in vivo.

Amino Acid Sequence↗

In vitro antibacterial activity of FK037, a novel parenteral broad-spectrum cephalosporin.

FK037 is a new parenteral cephalosporin, which offers some advantages over the commercially available parenteral cephalosporins. It demonstrated potent broad-spectrum activity against clinical isolates of Gram-positive bacteria including methicillin-resistant staphylococci, and Gram-negative bacteria including Pseudomonas aeruginosa. Against clinical isolates of aerobic Gram-positive bacteria, FK037, like cefpirome, demonstrated more potent activity than ceftazidime, cefoperazone and ceftizoxime. It is noteworthy that FK037, on the basis of the MIC90s, was the most active of all the cephalosporins tested against methicillin-resistant Staphylococcus aureus (MRSA). It was similar in activity to cefpirome against methicillin-sensitive S. aureus (MSSA). Against clinical isolates of aerobic Gram-negative bacteria, FK037, like cefpirome, was superior to cefoperazone, similar to ceftazidime and inferior to ceftizoxime in activity. Against P. aeruginosa, FK037 was superior to cefoperazone, similar or slightly superior to cefpirome and inferior to ceftazidime in activity. However, FK037 exhibited significant activity against Citrobacter and Enterobacter which were highly resistant to ceftazidime, cefoperazone and ceftizoxime. FK037 had an advantage in that its bactericidal activity against S. aureus, Escherichia coli and P. aeruginosa at sub-MICs (1/2 or 1/4 the MIC) was much stronger than those of cefpirome and ceftazidime. Moreover, it exhibited potent bactericidal activity against MSSA, MRSA and P. aeruginosa in a pharmacokinetic in vitro model simulating human plasma concentrations after intravenous dosage of 0.125, 1.0 and 1.0 g, respectively. FK037 inhibited essential penicillin-binding proteins (PBPs), 1, 2 and 3 of S. aureus with a 50% inhibitory concentration (I50) of 0.58 micrograms/ml or lower. Of essential PBPs 3, 1a and 1b of E. coli and P. aeruginosa, FK037 inhibited PBP 3 at the lowest I50 (0.03 and 0.04 micrograms/ml, respectively) and PBPs 1a and 1b with I50 values of 2.7 micrograms/ml or lower. FK037, like cefpirome, was highly stable to hydrolysis by various beta-lactamases except Ic cephalosporinase from Bacteroides fragilis, and had extremely low affinity for beta-lactamases. Therefore, FK037 was more potent than ceftazidime in activity against beta-lactamase-producing bacteria except P. aeruginosa and Serratia marcescens. The ability of FK037 to penetrate the outer membrane of E. coli was slightly higher than that of ceftazidime, but slightly lower than that of cefpirome.

Anti-Bacterial Agents↗

Excellent activity of FK037, a novel parenteral broad-spectrum cephalosporin, against methicillin-resistant staphylococci.

FK037 exhibits potent in vitro and in vivo antibacterial activity against methicillin-resistant staphylococci. In in vitro studies, FK037 was the most active of the cephalosporins and imipenem tested against the highly methicillin-resistant staphylococci (MIC > 100 micrograms/ml). Only 2 of 57 strains of highly methicillin-resistant Staphylococcus aureus (H-MRSA) had a FK037 MIC value of 50 micrograms/ml. On the other hand, 55, 40 and 19 strains had MICs of 50 or > or = 100 micrograms/ml to cefpirome, flomoxef and imipenem, respectively. Against 13 strains of highly methicillin-resistant coagulase-negative staphylococci (H-MRCNS), FK037 inhibited all the strains at < or = 50 micrograms/ml, but there were many strains highly resistant to the reference drugs with MICs of > or = 100 micrograms/ml. The influence of culture conditions such as low temperature, high inoculum and supplementation with 4% NaCl on the anti-MRSA activity of FK037 was less than those with cefpirome, flomoxef and imipenem. The in vitro frequency of spontaneous mutant cells highly resistant to FK037 in MRSA was lower than that to cefpirome and flomoxef. These findings were supported by lack of colonies inside the inhibition zone demarcated by FK037 in a disk sensitivity test, although many colonies proliferated inside the inhibition zone demarcated by flomoxef and imipenem. The increase in MIC of FK037 against a MRSA strain during subculture in the presence of the drug was smaller than that noted with the reference drugs. FK037 had higher affinity and faster binding for the PBP 2a of MRSA than that of the reference drugs. Moreover, the capacity to induce PBP 2a was lower for FK037 than that of cefpirome but higher than that of flomoxef. In an in vitro pharmacokinetic model simulating human plasma concentrations, FK037 showed potent bactericidal activity against H-MRSA in the plasma concentrations after intravenous infusion dosing with 1.0 g. FK037 was synergistically active against H-MRSA in combination with either imipenem of fosfomycin. The in vitro post-antibiotic effect (PAE) of FK037 against H-MRSA ranged from 1.2 to 1.7 hours at one to four times the MIC. FK037 had potent therapeutic effects against lethal systemic infections and experimental local infections in mice such as pneumonia, endocarditis, subcutaneous abscess, intrauterine infection and granuloma pouch infection due to MRSA or methicillin-resistant Staphylococcus epidermidis (MRSE). FK037 was about 4, 8 and 1.5 times more effective than cefpirome, flomoxef and imipenem, respectively, against lethal systemic infections with H-MRSA.(ABSTRACT TRUNCATED AT 400 WORDS)

Abscess↗

[Sleep-disordered breathing in Japan: an overview].

Questionnaires were answered by 3,243 presumably healthy subjects who underwent regular medical checkups in four cities. The prevalences of risk factors for sleep-disordered breathing (SDB) were as follows; habitual snoring was reported by 13-16%, excessive daytime sleepiness by 8-9%, insomnia by 7-13% and systemic hypertension by 5-13%. Polysomnographic studies performed on some possible SDB cases who were selected by the presence of risk factors estimated that the average prevalence of SDB in the present population would be in the range of 1.14-1.94%. Secondly, questionnaires were sent to the main hospitals and institutes involved in the management of patients with SDB, asking about diagnostic criteria, number of SDB patients, management, effectiveness of treatment, etc. The total number of patients registered at those hospitals was 2,751 in 1991. Of the 132 patients who were followed for more than six months, the efficacies of body weight loss, medications, nasal CPAP and UPPP were compared. Based on the analyses of the 279 patients examined some tentative vriteria for diagnosis and for treatment are proposed.

Female↗

[Criteria for clinical evaluation of antibiotics in pediatrics. The purpose and process for establishing the criteria].

This paper describes the purpose and process for establishing "Criteria for Clinical Evaluation of Antibiotics in the Pediatric Field", which was reported in the Japanese Journal of Antibiotics Vol. 46, May, 1993. The Criteria Committee was organized in November 1991. Four meetings were held to establish the draft criteria. The criteria were applied to the evaluation of oral cephem S-1108 and parenteral cephem SCE-2787. When the criteria were compared with the conventional criteria, the results indicated that no difference was obtained in the efficacy rate as a whole, the sum of "Good" and "Excellent" cases, but there was a difference in the cases judged to be "Excellent". Partial alteration was made to the draft criteria and the Committee produced the final version of the criteria. However, the criteria are far from complete, so it will be subjected to further revision it accordance with future advance in chemotherapy.

Bacterial Infections↗

[Long-term artificial ventilation by nasal intermittent positive pressure ventilation; 6 cases of domiciliary assisted ventilation].

Six patients with chronic respiratory failure associated with hypercapnia were treated with nasal intermittent positive pressure ventilation (NIPPV) at home. NIPPV was delivered via a custom molded nasal interface described by McDermott. The patients consisted of one patient with kyphoscoliosis, three with Tb-sequela, one with COPD, and one with neuromuscular disease. Each patient had been treated with oxygen therapy until assisted ventilation was initiated because of CO2 retention. NIPPV was administered using a volume cycled flow generator set to deliver a minute volume such that PaCO2 was maintained between 35 and 45 Torr on NIPPV trial performed during wakefulness under the condition of no leakage from the mask. Supplementary oxygen was added so that oxygen saturation was maintained above 90 percent during more than 95% of nighttime NIPPV. Arterial blood gas tensions during daytime spontaneous breathing showed an improvement (PaCO2 68.3 +/- 7.2 Torr, PaO2 70.4 +/- 15.5 Torr, SaO2 91.6 +/- 4.3% before treatment; PaCO2 55.8 +/- 4.7 Torr, PaO2 87.5 +/- 16.5 Torr, SaO2 95.5 +/- 1.7% on treatment, mean +/- SD). The duration of NIPPV at home ranged from 2 to 24 months (11.7 +/- 6.8), and there was no hospitalization due to exacerbation during this period. In conclusion, NIPPV via a custom molded mask is simple, noninvasive, and suitable for the provision of long-term and domiciliary assisted ventilation.

Adult↗

Potential errors in measuring the phase difference between chest flow and mouth flow.

We have previously reported that the phase difference between chest and mouth flows was a useful indicator of obstructive lung disease. In this paper, we calculated the effects of (i) airway reactance, (ii) extrathoracic airway shunt impedance, (iii) heating and humidification of the inspired air, (iv) abdominal gas volume, and (v) respiratory quotient on the measurement of the phase difference between chest flow (Vc) and mouth flow (Vm) using computer simulations. When the airway impedance was approximated as simple airway resistance, the phase difference (theta r) was calculated to be 0.8% less than the phase difference (theta s) calculated from the airway impedance (Za), including airway inertance and shunt compliance, in the normal lung. theta s became larger than theta r when the peripheral resistance increased, but did not exceed 5%. The extrathoracic airway shunt impedance effect did not exceed 0.1%, regardless of the respiratory frequency, airway impedance or thoracic gas volume. The influence of heating and humidification of the inspired air on the phase difference was calculated to be within 5%. The effect of abdominal gas was highly dependent on the abdominal gas volume and the respiratory pattern, but was calculated to be within 5%. The influence of the respiratory quotient was calculated to be negligible. As a result, it was concluded that none of the factors discussed above are an obstacle to the clinical application of this method for the evaluation of pathological changes in obstructive airway disorders.

Airway Resistance↗

[Clinical studies on S-1108 in the field pediatrics].

Clinical studies on S-1108, a new oral cephem antibiotic, were carried out in the field of pediatrics. The following results were obtained. 1. The peak plasma level of S-1006 when administered after meal at a dose of 4 mg/kg was 2.47 micrograms/ml at an hour, and the serum half-life was 0.81 hour. The 4 hours urinary excretion rate of S-1006 was 35.7%. 2. S-1108 was administered to 15 children with various infections (3 patients with pneumonia, 3 with acute bronchitis, 4 with scarlet fever, 2 with acute tonsillitis, 1 with phlegmon and 2 with urinary tract infections). The overall clinical efficacy rate was 100%. 3. Side effects or abnormal laboratory test values were not observed except for diarrhea in 1 and eosinophilia in 1.

Absorption↗

Dynamic control of breathing during exercise and hypercapnia.

The dynamic influences of end-tidal CO2 and exercise on ventilation are compared when CO2 and exercise are imposed separately and when they are imposed simultaneously. Five human subjects are studied. The subjects performed three trials: random work rate forcing, random CO2 inhalation and their simultaneous loading. The work rate was varied between 20 and 80 W as a pseudorandom binary sequence. The concentration of inspired CO2 was varied randomly between 0 and 7 per cent, adjusted so that it produced approximately the same amount of ventilatory fluctuations as the random work load. The relative contribution of each variable was analysed using multivariate autoregressive analysis at frequencies ranging from 0.1 to 1 cycle min-1. The results show that the dynamics of the response to CO2 inhalation, exercise and their combination are nonlinear and that the combination of CO2 inhalation and exercise magnifies the nonlinear behaviour. Ventilation is largely unaffected by either work rate or end-tidal CO2 at 1 cycle min-1. During simultaneous CO2 and work rate forcing, ventilation tends to follow the change in the end-tidal CO2.

Adult↗

Phase differences between chest and mouth flows in patients suffering from pulmonary disease.

The phase difference (PD) between mouth flow and chest flow during rest breathing was measured in pulmonary diseased patients using a body box and the results were compared with normal subjects. Whereas the PD increased in patients with chronic pulmonary obstructive disease (COPD) compared to normal subjects, PD was found to be normal in patients with interstitial pulmonary fibrosis (IPF) (Normal: 2.94 +/- 1.25, COPD: 11.32 +/- 4.17*, IPF: 2.62 +/- 1.67 degrees; *P < 0.01). PD correlated well with FEV1.0/VC%, PFR, RV/TLC, VTG and Ra (r: -0.759, -0.672, -0.788, 0.666, 0.606). From an in-depth analysis of the results, we suggest that the factors which increase PD in COPD patients include hyperinflation of the lung, increases in airway resistance and increases in the parallel inhomogeneity of airway resistance accompanied by an unevenness of alveolar pressures. PD was thought to be clinically useful for the evaluation of the pathological stages of COPD because it reflects the overall clinical manifestations in COPD patients.

Adult↗

Primary structures of sardaines Z1 and Z2, protamines isolated from striped bonito (Sarda orientalis).

Striped bonito protamine, sardaine, was isolated from the sperm of striped bonito (Sarda orientalis) by extraction with sulfuric acid followed by ion-exchange chromatography. The preparation gave a single band upon polyacrylamide gel electrophoresis. Sardaine consists of 34 amino acid residues, and its sequence is: Pro-Arg-Arg-Arg-Arg-Arg-Ser(Ala)-Ser-Arg-Pro-Val-Arg-Arg-Arg-Arg-Arg-Tyr -Arg- Arg-Ser-Thr-Ala-Ala-Arg-Arg-Arg-Arg-Arg-Val-Val-Arg-Arg-Arg-Arg. At position 7, serine (sardaine Z1) is partially replaced by alanine (sardaine Z2). The ion spray mass spectrum shows that sardaines Z1 and Z2 have molecular masses of 4,612.49 and 4,596.09 Da, respectively. The sequence of sardaine Z1 is 100% identical with that of thynnine Z2 from tuna fish (both fish belong to Scombridae, Perciformes).

Amino Acid Sequence↗

[Hyperventilation syndrome].

Of 16 patients with hyperventilation syndrome (HVS), 11 experienced hypoxemic episodes (defined as PaO2 < or = 60 Torr or SaO2 < or = 90%). To investigate the relationship between hypoxemia in HVS patients and their hypoxic ventilatory response (HVR), we examined 9 of 11 HVS patients who experienced hypoxemic episodes after acute hyperventilation attacks. In order to investigate the genesis of hypoxemia after hyperventilation, we also examined minute ventilation and visual analog scale (VAS) scores representing the sensation of dyspnea at the start and at 70% arterial O2 saturation (SaO2) during HVR in 9 normal subjects under isocapnia and hypocapnia following voluntary hyperventilation (VHV). The HVR of 9 HVS patients who experienced hypoxemic episodes was normal. In 9 normal subjects, minute ventilation and VAS scores representing the sensation of dyspnea at 70% SaO2 during HVR were higher under isocapnia than under hypocapnia following VHV (p < 0.01). VAS scores taken during the HVR immediately following VHV and at 70% SaO2 were not significantly different. HVR and VAS scores representing the sensation of dyspnea were decreased under hypocapnia following VHV. These reductions were thought to be the main factors responsible for the genesis of hypoxemia following acute hyperventilation attacks in HVS patients. We conclude that hypoxemia is an important clinical sign in HVS patients, and it is important to investigate the breathing and chemical drive under hypocapnia, in order to understand the chemical regulation of breathing in HVS patients.

Adult↗

[Evaluation of chemotherapy of unresectable non-small cell lung cancer].

For this evaluation, a comparison was made of survival of 34 patients with non-small cell lung cancer who had undergone chemotherapy (Group B) with that of 38 patients without this chemotherapy (Group A). Group B had received neither radiotherapy for primary lesions nor bronchial artery infusion of anticancer drugs, and the chemotherapeutic regimen was CDDP + VDS or CDDP + VDS + MMC chemotherapy. MST of this group was significantly longer than that of Group A (4.5 months vs 7.3 months. P less than 0.01), but the PS features of the two groups differed significantly. A comparison was thus made of survival for PS 1-2 cases in both groups (Group A: 17 cases, Group B: 27 cases). MST of group A and B were 6.8 and 9.8 months, respectively (P less than 0.05). The efficacy of the treatment for prolonging survival in terms of age, sex, PS, histology, T factor, N factor and M factor was evaluated by multivariate analysis using the proportional hazard model of Cox. The results obtained indicated the chemotherapy significantly prolonged survival.

Aged↗

[Function, molecular structure and gene expression of interleukin-1].

Recent cloning of human and murine IL-1 receptor (IL-1R) has revealed that there are at least two type of IL-1R: type I IL-1R is detected on T cells and fibroblasts and consists of 552 AAs with a cytoplasmic domain of 213 AAs, while type II is detected on B cells and monocytic cell lines and consists of 398 AAs with a short stretch intracytoplasmic domain of 29 AAs. Extracytoplasmic portion of IL-1R has some homology with vaccinia virus B15 Ag or fibroblast protein ST-2, while cytoplasmic portion has considerable similarity with Drosophila toll gene. By transfecting murine type I IL-1R cDNA into a human Jurkat cell line, structural and functional potion required for the IL-1 signal transduction is determined. At least broad portion of cytoplasmic domain including 364-474 AAs from N-terminus are found to be essential, while PKC acceptor site (Ser-431 and Ser-509), and PKA acceptor site (Ser-528) are not essential for the IL-8 gene expression.

Amino Acid Sequence↗

[Laboratory and clinical studies on cefprozil in the field of pediatrics].

Laboratory and clinical studies on cefprozil (CFPZ, BMY-28100), a new cephem antibiotic, were carried out in the field of pediatrics. The results obtained are summarized as follows: 1. Serum concentrations, urinary concentrations and urinary recovery rates of CFPZ were determined upon oral administration of CFPZ after meal at doses of 4 mg/kg granules in a case, 7.5 mg/kg granules in 2 cases and 15 mg/kg granules in one. Peak serum levels of CFPZ were obtained at an hour in 3 cases and at 2 hours in 1 case after administration of the drug with a range of 2.7-8.6 micrograms/ml with half-lives of 0.69-0.95 hours. Urinary recovery rates in the first 6 hours after administration ranged from 59.4-71.3%. 2. MICs of CFPZ against 36 clinical isolates (Staphylococcus aureus 4 strains, Streptococcus pneumoniae 5, Streptococcus pyogenes 5, Escherichia coli 5, Haemophilus influenzae 12, Haemophilus parainfluenzae 4, and Branhamella catarrhalis 1) were compared with those of cefaclor (CCL) and ampicillin (ABPC). The antibacterial activity of CFPZ was superior to those of CCL against Gram-positive cocci, and to those of ABPC against E. coli, and was equal to those of CCL and inferior to those of ABPC against H. influenzae. 3. Thirty-seven pediatric patients with acute infectious diseases (pharyngitis/tonsillitis 17, bronchitis 7, pneumonia 3, skin and soft tissue infection 2, and urinary tract infection 8) were treated with CFPZ at daily doses of 10-47 mg/kg t.i.d. as a rule. The efficacy rates were 100% clinically and 56% bacteriologically. 4. Side effects or abnormal laboratory test values were not observed except for an increased platelet count in 1 case and elevated GOT, GPT values in 2 cases.

Bacteria↗