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Biomedical subjects

I Nishi

Publications and source records attributed to I Nishi.

At least 19 recordsLinked to original sources

In vitro combined effects of cefozopran/teicoplanin and cefozopran/vancomycin on methicillin-resistant Staphylococcus aureus.

We determined the in vitro effects of teicoplanin (TEIC) or vancomycin (VCM) added to cefozopran (CZOP) on 50 methicillin-resistant Staphylococcus aureus (MRSA) strains, using a modified checkerboard method with serial 1.25-fold dilutions, and assessed the time-kill curve. CZOP + TEIC was synergistic (fractional inhibitory concentration index < or = 0.5) against 98% and CZOP + VCM against 20% of strains. Both drug combinations were additive against the remaining strains. A comparison of the fractional bactericidal concentration indices for 32 strains showed synergistic bactericidal effects for CZOP + TEIC in 88%, and in 48% for CZOP +VCM, confirming that CZOP + TEIC is superior to CZOP + VCM. The time-kill curve confirms that the bactericidal potency of these drugs is increased through combined use with CZOP. These results suggest that treatment using TEIC or VCM with CZOP may be useful in treating MRSA infections, including polymicrobial infections and those involving Gram-negative rods.

Anti-Bacterial Agents↗

Neonatal presentation of adult-onset type II citrullinemia.

Adult-onset type II citrullinemia (CTLN2) is characterized by a liver-specific argininosuccinate synthetase deficiency caused by a deficiency of the citrin protein encoded by the SLC25A13 gene. Until now, however, no SLC25A13 mutations have been reported in children with liver diseases. We described three infants who presented as neonates with intrahepatic cholestasis associated with hypermethioninemia or hypergalactosemia detected by neonatal mass screening. DNA analyses of SLC25A13 revealed that one patient was a compound heterozygote for the 851de14 and IVS11+IG-->A mutations and two patients (siblings) were homozygotes for the IVS11+lG-->A mutation. These results suggested that there may be a variety of liver diseases related to CTLN2 in children.

Adult↗

Using isoproterenol stress echocardiography to predict the response to carvedilol in patients with dilated cardiomyopathy.

Trials have demonstrated that carvedilol can produce hemodynamic, symptomatic, and prognostic improvements in dilated cardiomyopathy (DCM), but some DCM patients have deteriorated after carvedilol, developing congestive heart failure. The present study investigated the use of isoproterenol (ISP) stress echocardiography to select those patients with DCM who would respond to carvedilol. ISP was infused intravenously in 22 patients with DCM and they were classified into 2 groups based on the left ventricular systolic response: good response to ISP [change in fractional shortening (FS) with ISP > 0.05, n=13] and poor response to ISP (change < or = 0.05, n=9). In the good response group, FS significantly increased from 0.12+/-0.04 to 0.17+/-0.08 (mean+/-SD, p<0.05) with carvedilol, and 7 patients improved symptomatically (New York Heart Association class). However, in the poor response group, no significant difference was observed between FS at baseline and that at the end of follow-up. Moreover, only 1 patient in the poor response group improved symptomatically. ISP stress echocardiography can assist in selecting patients with DCM who will respond positively to carvedilol.

Adrenergic beta-Antagonists↗

Impaired ability to secrete atrial natriuretic peptide in response to isoproterenol infusion in patients with dilated cardiomyopathy.

OBJECTIVES: The myocardium has 2 functions in vivo, that of pump and endocrine organ. Therefore, simultaneous examinations of cardiac systolic reserve and endocrine reserve are important in evaluating the activities of the myocardial cells. This study investigated the relationship between cardiac systolic reserve and secretion of atrial natriuretic peptide (ANP) in response to isoproterenol infusion in patients with dilated cardiomyopathy. METHODS: Isoproterenol was infused intravenously in 6 healthy individuals (control group) and 32 patients with dilated cardiomyopathy. The left ventricular systolic responses and plasma ANP concentrations were measured. RESULTS: Patients with dilated cardiomyopathy were classified into 2 groups: patients with a good response (change in fractional shortening > 7%, 17 patients) and those with a poor response (change in < or = 7%, 15 patients). There was no significant difference in end-diastolic dimension, fractional shortening, heart rate, or systolic blood pressure between the 2 groups of patients with dilated cardiomyopathy at rest. The resting plasma ANP concentration in the poor-response group (88.8 +/- 59.0 pg/ml) was significantly higher than that in the other 2 groups (good: 47.0 +/- 35.9 pg/ml, p < 0.05, control: 9.8 +/- 4.1 pg/ml, p < 0.01, respectively). The percentage change in ANP after isoproterenol infusion in the poor-response group (-7.1 +/- 16.7%) was significantly less than that in the other 2 groups (good: 12.6 +/- 27.3%, p < 0.05, control: 31.5 +/- 24.6%, p < 0.01, respectively). CONCLUSIONS: The resting plasma ANP concentration can be used to evaluate the cardiac systolic reserve in patients with dilated cardiomyopathy. Decreased myocardial systolic reserve is also associated with impaired ability to secrete ANP.

Adrenergic beta-Agonists↗

[Informed consent for the use of the remaining portion of laboratory specimens for education, research, and quality control of laboratory tests].

The remaining portion of a laboratory specimen is usually used for education, research, and quality control of laboratory tests in hospitals, but informed consent has not been obtained because of the high volume of patients who undergo laboratory tests. However, patients must be informed in some manner. Therefore, we decided to inform patients that any remaining specimen would be used for various purposes by placing such a notice on walls in the central clinical laboratory and hospital lobby. We then obtained a signature on a dissent document, instead of a consent document, from any patient who dissented from such use. This indirect process for obtaining informed consent was approved by the ethics committee of Osaka University Medical School. The number of dissent documents sent in to the director was 54 of about 400,000 patients who underwent laboratory tests over the last 3 years, and there was no complaint against this "informed consent process".

Clinical Laboratory Techniques↗

Identification of two novel mutations in the SLC25A13 gene and detection of seven mutations in 102 patients with adult-onset type II citrullinemia.

Adult-onset type II citrullinemia (CTLN2) is characterized by a liver-specific deficiency of argininosuccinate synthetase (ASS) protein. We have recently identified the gene responsible for CTLN2, viz., SLC25A13, which encodes a calcium-binding mitochondrial carrier protein, designated citrin, and found five mutations of the SLC25A13 gene in CTLN2 patients. In the present study, we have identified two novel mutations, 1800ins1 and R605X, in SLC25A13 mRNA and the SLC25A13 gene. Diagnostic analysis for the seven mutations in 103 CTLN2 patients diagnosed by biochemical and enzymatic studies has revealed that 102 patients had one or two of the seven mutations and 93 patients were homozygotes or compound heterozygotes. These results indicate that CTLN2 is caused by an abnormality in the SLC25A13 gene, and that our criteria for CTLN2 before DNA diagnosis are correct. Five of 22 patients from consanguineous unions have been shown to be compound heterozygotes, suggesting a high frequency of the mutated genes. The frequency of homozygotes is calculated to be more than 1 in 20,000 from carrier detection (6 in 400 individuals tested) in the Japanese population. We have detected no cross-reactive immune materials in the liver of CTLN2 patients with any of the seven mutations by Western blot analysis with anti-human citrin antibody. From these findings, we hypothesize that CTLN2 is caused by a complete deletion of citrin, although the mechanism of ASS deficiency is still unknown.

Adolescent↗

Pulmonary tissue volume measured by acetylene rebreathing under artificial ventilation.

OBJECTIVE: In order to evaluate the pulmonary congestive state of patients being mechanically ventilated, an acetylene rebreathing method was employed. Measurement of pulmonary tissue volume by the acetylene (C2H2) rebreathing method was performed in 15 patients under artificial ventilation including four congestive heart failure cases, one renal failure case, and 12 healthy controls. METHODOLOGY: The subjects rebreathed mixed gas containing 0.65% C2H2, 10% argon (Ar), and 60% oxygen (O2) from end-tidal level, and inspiratory and expiratory gas concentrations were measured by a mass spectrometer. Correction for system volume reduction during rebreathing due to gas exchange and C2H2 concentration fluctuation was performed, pulmonary tissue volume was calculated from the C2H2 and Ar concentration difference at the time zero intercept. Time zero was assumed to be the time at which C2H2 and Ar concentration started to differ. RESULTS: Pulmonary tissue volume per functional residual capacity and pulmonary tissue volume per pulmonary capillary blood flow for cases with congestive heart failure and renal failure cases were significantly higher than those for non-pulmonary congestion cases and normal controls. CONCLUSION: The measurement of pulmonary tissue volume by C2H2 rebreathing can be applied to the patients under artificial ventilation in order to quantitatively evaluate pulmonary congestion or edema.

Acetylene↗

Simultaneous continuous 13C, 12C analysis of expired gas in the 13C breath test.

The 13C breath test is a method of clarifying the metabolism of loaded substances by administering 13C-labelled materials and calculating the 13CO2 and 12CO2 ratio (13C/12C isotope ratio) in the expired gas. The materials are metabolized and expelled in the expired gas. Because simultaneous continuous measurement of 13CO2 and 12CO2 in expired gas has been difficult up to the present, respective expired gases, including dead space before and after administration, have been sampled to separate sampling bags and 13C/12C has been measured in the bags and changed fraction of 13C/12C after administration (delta) has been used to judge the metabolic process. This method is affected by the contamination of the dead space gas. In the present study, in order to exclude the dead space effect, simultaneous continuous analysis of 12CO2 and 13CO2 of expired gas identifying alveolar gas was applied to the 13C-urea breath test in addition to the conventional sampling bag method. Both isotope detectors were attached to a mass spectrometer. Fifty-six cases receiving stomach health check-ups for Helicobacter pylori were examined. Delta was calculated in the bag or in phase III of continuous gas measurement. Because the bag contains dead space, delta was reduced and sensitivity and specificity with reference to gastric fluoroscopy or Helicobacter pylori IgG antibody were reduced. Decreasing the dead space contamination is important in reducing the measurement error in the 13C breath test and simultaneous continuous measurement is a good tool for this purpose.

Adult↗

Impaired peripheral vasoconstriction in response to alpha-adrenergic stimulation in patients with idiopathic hypertrophic cardiomyopathy.

Exercise hypotension has been documented in patients with hypertrophic cardiomyopathy (HCM). Some investigators reported that this is due to an inadequate increase of systemic vascular resistance during or after exercise. The aim of this study was to investigate the pathogenesis of limb vascular response abnormalities in patients with idiopathic HCM. Thirteen patients with HCM and 9 healthy controls were administered an endothelium-dependent dilator (acetylcholine), a direct smooth muscle dilator (nitroglycerin), an alpha-adrenergic stimulator (phenylephrine), and a beta-adrenergic stimulator (isoproterenol) by intra-arterial infusion. Peripheral vascular resistance was assessed by forearm plethysmography at rest and during each infusion to obtain the percentage change in vascular resistance. Isoproterenol, acetylcholine and nitroglycerin produced dose-related vasodilatation with no significant differences between HCM patients and healthy controls. The percentage increase in vascular resistance was significantly less in HCM patients than in healthy controls after phenylephrine infusions of 0.5 microg/min (155+/-38% vs 195+/-47%, mean+/-SD, p<0.05) and 1.0 microg/min (174+/-49% vs 238+/-65%, p<0.05). Vasoconstriction mediated by alpha-adrenergic receptors appeared to be impaired in the peripheral vasculature of patients with HCM.

Adrenergic alpha-Agonists↗

Improved fatigue resistance not associated with maximum oxygen consumption in creatine-depleted rats.

Effects of feeding of either creatine or its analog beta-guanidinopropionic acid (beta-GPA) on endurance work capacity and oxygen consumption were studied in rats. Resting high-energy phosphate contents in hindlimb muscles were lower in the beta-GPA group and higher in the creatine group than in controls. The glycogen contents in resting hindlimb muscles of rats fed beta-GPA were significantly higher than those in controls. The endurance run and swimming times to exhaustion were significantly greater (32-70%) in the beta-GPA group than in the control and creatine groups. However, there were no beneficial effects on the maximum oxygen consumption (VO2max) and oxygen transport capacity of blood by the feeding of beta-GPA. None of these parameters were significantly influenced by creatine supply. Both maximum exercise time and VO2max in the beta-GPA group were not changed by normalization of glycogen levels. The activities of mitochondrial enzymes in skeletal muscles were higher in the beta-GPA group than in the controls. Thus endurance capacity is improved if the respiratory capacity of muscles is increased, even when the contents of high-energy phosphates in muscles are lower. Increased endurance capacity was not directly associated with the elevated levels of muscle glycogen, oxygen transport capacity of blood, or VO2max.

Animals↗

[Use of acetylene rebreathing to measure pulmonary tissue volume in patients undergoing hemodialysis].

Acetylene rebreathing was used to measure pulmonary tissue volume in 10 normal subjects and in 15 patients undergoing hemodialysis. A mixture containing 0.65% acetylene and 10% argon was rebreathed from the end-tidal level, and gas concentrations were measured with a mass spectrometer. Pulmonary tissue volume was computed from the difference between the argon equilibrium concentration and the corrected acetylene concentration, under the assumption that FAr was constant. Measured tissue volumes per unit lung volume (at functional residual capacity) in the normal subjects, before hemodialysis, and after hemodialysis were 0.204 +/- 0.042, 0.334 +/- 0.100, and 0.282 +/- 0.074, respectively. Tissues volumes per unit lung volume were significantly higher in the patients than in the normal subjects, even after hemodialysis. Tissues volumes per unit of lung volume decreased significantly during hemodialysis. Pulmonary blood flows per unit of body surface area of normal subjects, before hemodialysis and after hemodialysis were 3.004 +/- 0.791, 2.790 +/- 1.007, and 2.399 +/- 0.781 (l/min/m2), respectively. These volumes did not differ significantly between normal subjects and patients, and they decreased significantly during hemodialysis. Measured tissue volumes per unit of pulmonary blood flow for normal subjects, before hemodialysis, and after hemodialysis were 0.119 +/- 0.034, 0.167 +/- 0.024, and 0.166 +/- 0.030 (1/1/min), respectively. The values in the patients did not change during hemodialysis, but they were significantly higher than the volumes in the normal subjects.

Acetylene↗

Development of photosynthesis and respiration measurement system using mass spectrometry.

A closed gas-exchange system was developed to measure gross photosynthesis and respiration discriminately and simultaneously. The system developed in this study included a high performance mass spectral analyzer for gas measurements. The gas-exchange system consisted of a 3L assimilation leaf chamber, a 1L flexible metallic bag, gas supply apparatus, and a lighting system. The lights were turned on and gas measurements were started after the initial 12CO2 concentration level was increased to 500 ppm. The 13CO2 gas was added to the chamber 10 min after the start of the light period. The lights were turned off 15 min after the addition of 13CO2. The 12CO2 and 13CO2 concentrations in the chamber during the light and dark periods were measured for pothos and maize leaves. The 13CO2 absorption rate by the leaves was larger than that for 12CO2 during the light period. It was assumed that the 13CO2 absorbed by photosynthesis was not evoluted by respiration during the first 25 min from the start of the light period. Based on this assumption, gross photosynthetic rate and respiration rate were estimated by calculating the difference in uptake rates of 12CO2 and 13CO2 during the light period.

Argon↗

Discriminating and continuous measurement of photosynthesis and respiration by monitoring 13CO2 and 12CO2 as tracers.

The simultaneous and discriminative measurement of the photosynthesis and the respiration of the plant was attained by simultaneous monitoring of 13CO2 and 12CO2 by artificial control of 13CO2 abundance of ambient air. The principle of the measurement is based on the following physiological processes. 6CO2 + 12H2O --> C6H12O6 + 6O2 + 6H2O, 6(13C)O2 + 12H2O --> (13C6)H12O6 + 6O2 + 6H2O, 6CO2 + 12H2(18O) --> C6H12O6 + 6(18O)18O + 6H20. Assuming that respiratory consumption of the new born carbon substrate fixed by photosynthesis is negligible during the measurement, the photosynthetic CO2 consumption VPCO2 and the respiratory CO2 production VRCO2 are measured according to the estimation (1) or (2), (1) for closed method, VPCO2 = k(V0 - V t)¿ F13CO2 + (F12CO2/F13CO2)F13CO2 ¿, VRCO2 = k(V0 - V t)¿ F12CO2 - (F12CO2/F13CO2)F13CO2 ¿, (2) for open method, VPCO2 = kVE ¿ (FI13CO2 - FE13CO2) + (F12CO2/F13CO2)(FI13CO2 - FE13CO2) ¿, VRCO2 = kVE ¿ (FI12CO2 - FE12CO2) - (F12CO2/F13CO2)(FI13CO2 - FE13CO2) ¿ where V0 is initial volume of growth chamber including attached flexible bag, FICO2 is the inlet or initial gas concentration of CO2 and FECO2 is the ambient gas concentration of CO2 in the chamber, V and VE are the sampling rate of mass spectrometer and the ventilation rate of the growth chamber respectively, k is the STPD conversion factor = ¿273(PB-PH2O)/760(273+tE)¿, tE(degrees C) is the ambient gas temperature. In the closed method, the gas container of the growth chamber is circulated, resulting FECO2 is varied according to the balance of consumption and production of CO2, while in the open method VE is controlled to keep FECO2 at a constant value. Both (1) and (2) methods were examined and evaluated on the measurements of komatsuna and maize.

Argon↗

[Intra-individual and seasonal variations of thyroid function tests in healthy subjects].

We report intra-individual and seasonal variations of thyroid function tests in healthy subjects. Blood samples were obtained from thirteen healthy males and seven healthy females every two weeks over a period of one year, and totally 25 samplings of each were made. Serum thyrotropin (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) were measured after the completion of the sampling. The 25 samples from each subject were always assayed with the same assay run. Variations of FT4 and FT3 in each subject were narrow and approximately one-third of normal reference ranges. The magnitude of individual variation of TSH values was proportional to the average of TSH in each individual. Serum TSH and FT3 values during winter were significantly higher than those during summer, but such change was not observed on serum FT4.

Adult↗

Novel thyrotropin (TSH)-TSH antibody complex in a healthy woman and her neonates.

A novel high-molecular-weight (MW) form of immunoreactive TSH [35,000 Da on Sephacryl S-200HR gel chromatography (S-200 chromatography)] was documented in a 32-year-old healthy woman who delivered two neonates with transient hyperthyrotropinemia. Her TSH levels ranged from 21.2 to 53.9 mU/L on different days or from 11.0 to 48.1 mU/L by the different immunoradiometric assay methods. The IgG fractions showed specific 125I-labeled hTSH binding and inhibited in vitro cAMP increase induced by hTSH but not that induced by bTSH. On protein G Superose HR affinity chromatography (protein G chromatography) equilibrated with 10 mmol/L sodium/potassium phosphate buffer (PB) followed by elution with 0.1mol/L glycine buffer, 95-99% of her TSH immunoreactivity eluted in the latter (bound) fraction while almost all was in the former (unbound) fraction in the control serum containing authentic hTSH. However, after dialysis of this bound fraction overnight with PB adding 0.5 mol/L NaCl (PB/NaCl), which exhibited greater ionic strength than PB, almost all TSH immunoreactivity changed from the bound fraction into the unbound fraction on the protein G chromatography equilibrated with PB/NaCl. These data indicate that the novel immunoreactive TSH was due to hTSH and hTSH-specific antibody complex, and dissociation of the complex may be incomplete on direct S-200. The immunoreactive TSH showed high MW form (35,000 Da). The dissociation may be almost complete during dialysis with greater ionic strength; the native TSH then appeared to be of formal size.

Adult↗

Differentiation of postpartum thyrotoxicosis by serum thyroglobulin: usefulness of a new multisite immunoradiometric assay.

Destruction-induced thyrotoxicosis and Graves' thyrotoxicosis must be differentiated, since they are treated differently. To find a useful marker, we examined serial changes in serum thyroglobulin (Tg) concentrations in 20 patients with postpartum thyroid disease (9, euthyroid Hashimoto's disease; 11, Graves' disease in remission in early pregnancy). Serum Tg was measured by a new multisite immunoradiometric assay that allows little influence of anti-Tg autoantibodies. Eight women developed destruction-induced thyrotoxicosis 1 to 4 months postpartum, 6 had relapse of Graves' thyrotoxicosis 2 to 4 months postpartum, and 6 remained euthyroid. In destruction-induced thyrotoxicosis, serum Tg 2 months before the onset was 13.3 +/- 11.4 micrograms/L, then clearly increased 1 month before (34.5 +/- 31.9 micrograms/L) and was even higher at the onset of thyrotoxicosis (116.5 +/- 137.1 micrograms/L). In contrast, serum Tg increased only at the onset in Graves' thyrotoxicosis (from 25.9 +/- 25.2 micrograms/L 1 month before to 76.1 +/- 75.3 micrograms/L at the onset, p < 0.05). There was no difference in serum Tg level at the onset between the two disorders. However, when data were expressed as the percent increase from the level one month before, and the cut-off value were taken at 150%, all 7 patients above the cut-off developed destruction-induced thyrotoxicosis, and 6 of 7 below had recurrent Graves' thyrotoxicosis. Thus, serial measurement of serum Tg is useful for the differentiation of destruction-induced thyrotoxicosis from Graves' thyrotoxicosis after delivery.

Adult↗

On-line determination of pulmonary blood flow using respiratory inert gas analysis.

An inert gas analysis method has been developed to perform on-line real time determination of pulmonary blood flow using a nonrebreathing approach. This technique is based on a mathematical model describing mass balance of two inert gases which are breathed using an open gas circuit. The measurements using this method are noninvasive, easy to peform, and do not disturb normal physiological processes. As well, since data are collected on a breath-by-breath basis, it is possible to estimate other respiratory, cardiopulmonary, and metabolic parameters simultaneously in a breath-by-breath manner. Special consideration was given to developing effective data processing algorithms to minimize the influence of measurement noise and respiratory variations. Experimental studies to compare this method with other accepted techniques were conducted to validate the present technique.

Acetylene↗