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Biomedical subjects

K Kuno

Publications and source records attributed to K Kuno.

At least 19 recordsLinked to original sources

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

[Laboratory and clinical studies on panipenem/betamipron in the field of pediatrics].

Laboratory and clinical studies on panipenem/betamipron (PAPM/BP), a new carbapenem antibiotic, were carried out in the field of pediatrics and the following results were obtained. 1. The antibacterial activities of panipenam (PAPM) against clinically isolated organisms in our department were high overall. 2. After 30 minutes intravenous infusion of PAPM/BP at a dose of 10 mg/10 mg/kg in 1 and of 20 mg/20 mg/kg in 2 children, peak plasma levels of PAPM ranged from 33.21 to 75.66 micrograms/ml at the end of the infusion. The half-lives were 0.81 to 0.93 hours. The cumulative urinary recovery rates in the first 6 hours after the start of drip infusion ranged from 10.7 to 40.4%. 3. PAPM/BP was administered to 16 pediatric patients with various infections. The clinical and bacteriological efficacy rates were both 100%. 4. No side effects were observed. Abnormal laboratory test results were also mild; slight elevation of GOT, GOT/GPT and eosinophylia in 1 each and thrombocytosis in 2.

Age Factors

[Laboratory and clinical studies on meropenem in pediatrics].

Laboratory and clinical studies on meropenem (MEPM), a new carbapenem antibiotic, were carried out in the field of pediatrics. The results obtained are summarized below. 1. The antibacterial activities of MEPM against clinically isolated organisms in our department were generally high. 2. After 30 minutes intravenous drip infusion of MEPM at a dose of 20 mg/kg to 2 children, the mean peak plasma level of MEPM was 32.7 micrograms/ml at the end of infusion with a mean half-life of 1.45 hours. The mean cumulative urinary recovery rate in the first 6 hours after infusion was 43.6%. 3. Fifteen patients with various bacterial infections were treated with MEPM. The clinical efficacy rate was 100% and the bacteriological efficacy rate was 95.2%. 4. No side effects were observed except in 1 case of mild diarrhea. Some abnormal laboratory test results were obtained, but they were mild with slight elevations of GOT and GPT in 2 cases.

Bacteria

[Therapy and clinical symptoms in patients with obstructive sleep apnea in Japan].

To investigate the long-term outcome of therapy and clinical symptoms of patients with OSAS (obstructive sleep apnea syndrome) in Japan, we studied 34 patients with OSAS who had been diagnosed by standard polysomnography more than one years (36.0 +/- 19.7 months: mean +/- SD) previously. They were 53.8 +/- 10.5 years old, body mass index was 27.8 +/- 5.2 kg/m2, and AHI (apnea & hypopnea index) was 50.0 +/- 24.2/h. The subjects had achieved weight loss (p less than 0.01), but had regained their initial weight at our follow-up. Eleven patients with OSAS were initially candidates for NCPAP (nasal continuous positive airway pressure), but only 5 patients used it for a prolonged time. The other 6 patients with OSAS could not use NCPAP because they did not wish to purchase a NCPAP instrument. One of 5 patients who used NCPAP for a long time died from lung cancer; thus, 4 patients used NCPAP continuously. Ten patients were commenced on ACZ (acetazolamide); however, only 5 patients took it continuously. ACZ resulted in some improvements in the sleep parameters (AHI index, desaturation time below SaO2 90%), but apnea & hypopnea duration and the difference in transcutaneous PCO2 between wake and sleep were not significantly improved by ACZ administration. ACZ was not as effective as NCPAP. Almost 60% of patients with OSAS had excessive daytime sleepiness. Hypertension was detected in about 60% of patients. Nine of 25 patients who had an automobile license had had more than one automobile accident. Nine patients who had had more than one automobile accident showed AHI greater than or equal to 30 in our study.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Traffic

[Application of nasal intermittent positive pressure ventilation to a case of limb-girdle muscular dystrophy].

We applied nocturnal ventilation (NV) with nasal intermittent positive pressure ventilation with custom molded mask (NIPPV-C Mclermott, 1989), as well as NV with tracheostomy intermittent positive pressure ventilation (TIPPV) to a male patient with limb-girdle muscular dystrophy who had developed chronic respiratory failure at the age of 47. NV with both methods successfully corrected nocturnal hypoxemia, improved daytime arterial blood gas values, and achieved a stable clinical course without marked deterioration for four years. Daytime PaO2 higher than 60 Torr and PaCO2 lower than 70 Torr while breathing room air were maintained with both methods, whereas PaO2 was lower than 50 Torr and PaCO2 higher than 70 Torr before the implementation of NV. TIPPV was safely suspended repeatedly for as long as two weeks, maintaining daytime PaO2 higher than 50 Torr. NIPPV-C was also repeatedly suspended for two weeks. Occasionally PaO2 dropped as low as 40 Torr after periods without NV; however, it was restored to higher than 60 Torr after one or two nights' NIPPV-C. These facts suggest that NV had a restorative effect on respiratory muscle fatigue in the present case. While on NIPPV-C, nighttime SaO2 was higher than 90% for 94% of the total time, and between 80% and 90% for the remaining 6% of the time. Desaturation for short periods was thought to be due to oral air leakage, which made the method slightly less effective than TIPPV. However, the overall clinical effectiveness of NIPPV-C was comparable to that of TIPPV.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease

Hepatitis B virus X protein transactivates human interleukin-8 gene through acting on nuclear factor kB and CCAAT/enhancer-binding protein-like cis-elements.

Interleukin-8 (IL-8) is a newly described leukocyte chemotactic and activating cytokine that belongs to the novel family of inflammatory cytokines whose genes locate on human chromosome 4, q12-21 region. The production of IL-8 is usually not constitutive and can be induced rapidly and abundantly in different cell types by a variety of stimuli such as lipopolysaccharide, interleukin-1, tumor necrosis factor-alpha as well as a tumor promotor phorbol myristate acetate. We report here that in addition to these stimuli the IL-8 gene can also be induced by the protein X of the hepatitis B virus (HBV-X) as evidenced by the enhanced IL-8 mRNA expression and IL-8 production observed in HBV-X-transfected cells. Furthermore, using several deletion mutants of the 5'-flanking regulatory region of the human IL-8 gene linked to the chloramphenicol acetyl transferase gene as a reporter, we have established here that both nuclear factor kB and CCAAT/enhancer-binding protein-like cis-elements located at -94 to -71 base pairs of IL-8 gene are essential and sufficient for the induction of the IL-8 gene by HBV-X. The same elements have been identified recently by us to be interleukin-1-, tumor necrosis factor-alpha-, and phorbol myristate acetate-responsive elements on the IL-8 gene. This suggests the existence of a common pathway for these inflammatory cytokines and HBV-X to activate the IL-8 gene. These observations might be relevant to the pathogenesis of inflammation in viral hepatitis.

Base Sequence

Evidence for binding of at least two factors, including T-rich strand-binding factor(s) to the single-stranded ARS1 sequence in Saccharomyces cerevisiae.

To study the mechanism of initiation of eukaryotic chromosomal replication, we examined protein factors interacting with the ARS1 region located near the centromere of chromosome IV in Saccharomyces cerevisiae. Using the gel shift assay, we found protein factor(s) which specifically bound to the T-rich strand of the region containing the core consensus and its flanking sequences in ARS1, but not to the opposite strand. We designated this factor ATS (ARS1, T-rich strand-binding factor(s]. Similar specific complexes were also detected with oligonucleotide probes specific for the H4 or C2G1 ARS. As we have previously identified another binding factor, we conclude that at least two factors bind to the single-stranded ARS1 sequence.

Base Sequence

Frequency characteristics of airway and tissue impedances in respiratory diseases.

We measured the frequency characteristics (at 10-40 Hz) of airway (Za) and tissue (Zt) impedances in cases of chronic obstructive pulmonary disease [asthmatic bronchitis (AB), chronic pulmonary emphysema (CPE)] and interstitial pneumonitis (IP) by use of an improved random noise oscillation and body box method. The results were then compared with those obtained for normal subjects. The real part of Za was markedly elevated in patients with AB but only slightly elevated in those with CPE. To interpret these data we used an electromechanical analogue including serial inhomogeneity with shunt impedance. From this model we concluded that AB causes both the central and peripheral airway resistances to increase, while CPE brings about a rise mainly in peripheral resistance. In IP patients, only the imaginary part of Zt decreased, which might reflect the decrease in both lung and chest wall compliance. In CPE patients, but not in AB patients, the real part of Zt fell. These data were consistent with the assumption that the decrease in mass per unit volume of lung tissue and hyperinflation of the chest wall in CPE patients might lower the tissue resistances.

Adult

[Laboratory and clinical studies on cefdinir (10% fine granules) in pediatric field].

Clinical studies on 10% fine granules of cefdinir (CFDN), a new cephem antibiotic, were carried out in the field of pediatrics. The results obtained are summarized as follows. 1. Half-lives of CFDN in plasma in 3 children when administered on an empty stomach were 1.77 hours (3 mg/kg per os) and 1.47 hours (6 mg/kg per os), respectively. Eight hour urinary excretion rates of CFDN were 21.5% (3 mg/kg per os) and 16.4% (6 mg/kg per os), respectively. 2. CFDN was administered to 11 children with various bacterial infections: 1 patient with scarlet fever, 1 with pharyngotonsillitis, 3 with acute bronchitis, 3 with pneumonia and 3 with urinary tract infections. The overall clinical efficacy rate was 90.9%. 3. Loose stool was noted in 1 patient. No abnormal laboratory test values were encountered.

Administration, Oral