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Biomedical subjects

H Inaba

Publications and source records attributed to H Inaba.

At least 127 records · Page 7Linked to original sources
PubMed1993

Chemiluminescence from bamboo shoot cut.

Bamboo shoot cut emitted weak light, which could be visualized with a two dimensional imaging system. A water extract of bamboo shoot contained tyrosine (a major component of total amino acids), bityrosine and peroxidase. Bamboo shoot peroxidase-H2O2-tyrosine system also emitted weak light with maxima at 490nm, 530nm and longer wavelength, identical to that in horseradish peroxidase-H2O2 system. Judging from these results, chemiluminescence from bamboo shoot cut might be originated from excited species generated by enzymatic oxidation of tyrosine and bityrosine.

Image Processing, Computer-Assisted↗
PubMed1993

Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A.

Hemophilia A is due to the functional deficiency of factor VII (FVIII, gene locus F8C). Although half the patients have no detectable FVIII protein in their plasma, the more rare patients (approximately 5%) have normal levels of a dysfunctional FVIII and are termed cross-reacting material (CRM)-positive. More commonly (approximately 45%), patients have plasma FVIII protein reduced to an extent roughly comparable to the level of FVIII activity and are designated CRM-reduced. We used denaturing gradient gel electrophoresis to screen for mutations within the F8C gene of 11 patients (6 CRM-positive, 5 CRM-reduced) and identified 9 different mutations in 9 patients after analyses of all 26 exons, the promoter region, and the polyadenylation site. Six mutations have not been described previously. Five were missense (Ser289Leu, Ser558Phe, Val634Ala, Val634-Met, Asn1441Lys), and the sixth was a 3-bp deletion (delta Phe652). A review of the literature and the assay of FVIII antigen in 5 hemophilia A patients with previously identified missense mutations from this laboratory yielded a total of 20 other unique CRM-reduced and CRM-positive mutations. Almost all CRM-positive/reduced mutations (24/26) were missense, and many (12/26) occurred at CpG dinucleotides. We examined 19 missense mutations for evolutionary conservation using the portions of the porcine and murine F8C sequences that are known, and 18/19 amino acid residues altered by mutation in these patients were conserved. Almost 50% of mutations (11/26) clustered in the A2 domain, suggesting that this region is critical for the function of FVIII.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

K252a, a potent protein kinase inhibitor, improves endotoxic lethality and glucose dyshomeostasis.

To investigate whether the inhibition of protein kinases including protein kinase C can antagonize endotoxicosis, the in vivo effects of K252a, a potent inhibitor of protein kinases, on endotoxin-induced lethality and glucose dyshomeostasis were determined in conscious rats. Sprague-Dawley rats (260-340 g) were divided into the following four groups: Group DS, 2.5% dimethyl sulfoxide (DMSO), 6 ml/kg iv + 0.9% saline, 2 ml/kg iv; group KS, K252a in 2.5% DMSO, 4 mg/kg iv + 0.9% saline; group DE, 2.5% DMSO + endotoxin (E. coli), 15 mg/kg iv; and group KE, K252a in 2.5% DMSO + endotoxin. A quarter of DMSO or K252a solution was continuously infused over a 15 min period before a bolus injection of either saline or endotoxin. The remaining dose was administered over a 180 min period after saline or endotoxin. All animals in the DS and KS groups survived for 24 hrs. K252a significantly improved endotoxic lethality. It attenuated the initial hyperglycemia, and late hypoglycemia, hyperlactacidemia, and base deficit after endotoxin. However, K252a had no influence on the endotoxic alterations of blood pressure, PaCO2 or PaO2. These results suggest that the activations of protein kinases, particularly protein kinase C, are involved in the pathogenesis of lethal endotoxicosis and sepsis.

Animals↗
PubMed1993

Spectra of the formaldehyde-induced ultraweak luminescence from yeast cells.

An increase in the intensity and distinct spectral changes of ultraweak luminescence from the yeast Saccharomyces cerevisiae were measured when the metabolism of cells was drastically altered. A small emission peak and a red emission band 680-850 nm appeared when air-dried cells were imbibed in water. Lethal concentrations of HCHO (0.01%-10%) elicited a 2500 fold increase of the emission intensity and distinct spectral alterations. A transient 500-580 nm emission appeared in the initial phase of interaction. Then a gradually increasing long-lasting red emission band centered around 620 nm predominated in the total spectral range covering 470-850 nm. These emissions were not correlated with minor changes in fluorescence emission and excitation spectra originating from tryptophan, flavins, and unidentified emitters.

Formaldehyde↗
PubMed1993

Modulation of protein kinase C alters hemodynamics and metabolism in the isolated liver in fed and fasted rats.

The activation of protein kinase C (PKC) has been implicated in the pathogenesis of gram-negative sepsis. The effects of PKC modulation on hepatic flow and metabolism were studied using isolated liver perfusion. The liver was isolated from well-fed or overnight-fasted, male Sprague-Dawley rats weighing 250-310 g, and perfused at a constant pressure of 12 cmH2O using a recirculating system. Phorbol 12-myristate 13-acetate (PMA), a potent activator of PKC, decreased hepatic flow and oxygen consumption, and increased net lactate production. It enhanced net glucose production in fed animals. Neither 4 alpha-phorbol didecanoate, an inactive phorbol ester for PKC nor 4 alpha-phorbol, an inactive phorbol had any significant effect. The effects of PMA were augmented by increasing calcium concentration in the medium. PMA at an initial concentration of 4 x 10(-8) M stimulated net lactate and/or glucose production more than a reduction of perfusion pressure from 12 to 6 cmH2O. Staurosporine, a potent PKC inhibitor, significantly attenuated the PMA-induced alterations of hepatic flow and oxygen consumption. These results indicate that modulation of PKC exerts significant effects on hepatic flow and metabolism, which are dependent on extracellular calcium concentrations and feeding conditions, and that the effect of PMA on carbohydrate metabolism is not merely attributed to decreases in hepatic flow and oxygen consumption. It is suggested that PKC activation may be involved in the alterations of hepatic flow and metabolism during severe sepsis.

Alkaloids↗
PubMed1993

Stability of transpedicle screwing for the osteoporotic spine. An in vitro study of the mechanical stability.

The influence of bone mineral density on the stability of transpedicle screwing was studied in the human cadaveric lumbar vertebrae. The pull-out force correlated with bone mineral density. The tilting moment (load needed to tilt the screw 4 degrees cranially at the screw-plate junction) and the cut-up force (load needed to tip the end plate up by the screw) correlated with bone mineral density. A correlation was also found between the maximum insertion torque of the screw and bone mineral density. The maximum insertion torque correlated with the pull-out force, the tilting moment, and the cut-up force. In the cyclic tilting test (200 cycles), the mean value of the tilting moment at the 200th cycle was 67.4 +/- 6.1%, compared with the first cycle. The results suggest that preoperative measurement of BMD is necessary for transpedicle screwing in osteoporotic cases, and that the cyclic tilting motion decrease its mechanical stability. The authors have also concluded that the maximum insertion torque could predict the mechanical stability.

Aged↗
PubMed1993

A convenient and inexpensive chemo-radiosensitivity assay for lung cancer cells using Terasaki's microplate.

We devised a simple in vitro sensitivity test for lung cancer cells using Terasaki's microplate. We used the test to screen for sensitivity to various carcinostatic drugs and radiation, and to determine the optimum method of administration. This assay has been used in routine clinical examinations because about 40% of non-small cell carcinoma and 80% of small cell carcinoma of the lung can be subcultured. We describe here our patients who underwent treatment, various sensitivity tests and the preparation of an optimal course of treatment based upon the results of the sensitivity tests. Cells were placed in primary culture as previously described for short-term selective culture, and 2nd-3rd generation subcultured cells were transferred to individual wells of Terasaki's microplates for various sensitivity tests. After culture for 10 days, the effect was evaluated using 0.1% iodonitrotetrazolium (INT). This test permits a variety of sensitivity tests and various studies of clinical models of intensive treatment to be performed conveniently and reproducibly, because subcultured cancer cells are used. Another advantage is that these cells can be applied to basic investigations, including the preparation of monoclonal antibodies and chromosomes, DNA ploidy and oncogene studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

[Antitumor activity of BOF-A2, a new 5-fluorouracil derivative, against human cancers xenografted in nude mice by intermittent administration].

Antitumor effects of BOF-A2 given intermittently was evaluated with human gastric (H-111, H-83), colorectal (H-110, H-143) and lung (H-74, LC-376) cancers xenografted in nude mice and compared with those by continuous administration. BOF-A2 was orally given 3 or 4 times per week at 30 or 35 mg/kg over 4 weeks. This drug was effective to 5 strains except H-110 (IR > or = 58%), remarkably effective to H-81 and H-143 (IR > or = 80%) and caused tumor regression in mice bearing H-81 especially. Moreover, the drug was effective to H-74 which is rather insensitive to 5-FU and its known derivatives. When the drug was given orally to nude mice xenografted LC-376, 5-FU levels in the tumor tissue was notably durative for a long time as compared to UFT. It would be concluded that BOF-A2 was much effective to insensitive tumor to fluorinated pyrimidines or other anticancer, because of persistence of high levels of 5-FU in the tumor tissue. On the other hand, diarrhea which is caused by other fluorinated pyrimidines or consecutive administration of BOF-A2, was mild by the intermittent administration of BOF-A2.

Administration, Oral↗
PubMed1993

Phase 1 study of L-627, biapenem, a new parenteral carbapenem antibiotic.

The safety and pharmacokinetics of L-627, a new injectable carbapenem antibiotic, were evaluated in healthy volunteers. In single-dose studies, 20, 40, 80, 150, 300 and 600 mg of L-627 were administered by i.v. infusions over 1 hour. Plasma concentration-time profiles were well described with a two-compartment open model. The half-life of elimination from plasma was 1.3 +/- 0.8 (mean +/- SD) hour, and the Cmax and AUC paralleled the doses given. The mean urinary recovery of unchanged L-627 within the first 12 hours was 63.1 +/- 2.7% of the dose. In the multiple-dose studies, 300 mg of L-627 (i.v. over 1 hour) was administered every 12 hours, 11 times in total and 600 mg of L-627 was administered every 12 hours, 9 times in total. No discernible accumulation of the drug in plasma was observed. There were no subjective or objective abnormal findings definitely attributable to the drug except that one subject in one of the multiple-dose regimens (300 mg b.i.d.) showed only a slight elevation of transaminase value, although the elevated value promptly recovered after completion of dosing. No abnormality was observed in the other multiple-dose regimen (600 mg b.i.d.). From these results, L-627 was concluded to be safe and well tolerated.

Adult↗
PubMed1992

Fluctuations in plasma levels of thrombomodulin in patients with DIC.

Plasma thrombomodulin (TM) has attracted considerable attention as a marker of endothelial cell membrane injury. We examined fluctuations in plasma TM levels in patients receiving therapy for the disseminated intravascular coagulation syndrome (DIC) using an enzyme immunoassay. Sixty healthy controls and 18 patients with DIC were studied. The mean +/- SD of the TM values initially measured immediately after the onset of DIC was 42.00 +/- 20.85 ng/ml, which was markedly increased as compared with the control value of 15.36 +/- 4.85 ng/ml (p < 0.001). Fluctuations in the TM levels over time were studied after dividing the patients according to the presence or absence of improvement in the underlying disease and improvement or lack thereof in the coagulation findings. Group I showed improvement in both categories, Group II showed improvement only in the latter, and Group III showed no improvement in either category. In Group I, the mean +/- SD of initial measured TM levels was 37.02 +/- 10.12 ng/ml and the mean of final values decreased to 58.9% of the initial value. This decrease was significant by paired Student's t-test (p < 0.01). The initial value in Group II was 45.86 +/- 18.86 ng/ml and the final values increased to 117.0% of the initial values, this difference was not significant. The initial value in Group III was 44.48 +/- 21.53 ng/ml and the final values increased to 143.4% of the former. This increase was significant by paired Student's t-test (p < 0.05). The difference in % fluctuations between Group I and Group III was significant by Wilcoxon's test (p < 0.01). These results suggest that the measurement of plasma TM can be useful in the management of DIC.

Adolescent↗
PubMed1992

Chemiluminescence in the crude extracts of soybean seedlings. Postulated mechanism on the formation of hydroperoxide intermediates.

It has been reported that weak chemiluminescence (CL) from crude extracts of soybean seedlings is remarkably enhanced with the addition of various aldehydes (Biochim. Biophys. Acta 1058, 209-216). The reactivity of certain emitter(s) with oxygen species was examined in the autoclaved extracts of seedlings. When samples were reduced by the addition of hydrosulfite, two different types of reactivities in CL were defined. One type showed an initial rapid increase and a subsequent fast decay in CL upon mixing with oxygen. This rapid increase in CL intensity was independent of the presence of aldehydes, and was significantly suppressed by SOD. However, the subsequent slow decay phase in CL was dependent on the presence of aldehydes. In the sample reduced more moderately by borohydride, the same slow decay of CL appeared upon mixing with acetaldehyde and oxygen. This second type of CL was not inhibited by active oxygen scavengers. Hydrogen peroxide added to unreduced (oxidized) samples also elicited CL. Three types of primary emitters may be oxidized to form transient hydroperoxide, and excited for light emission by slightly different ways: two of them are excited by abstraction of one atomic oxygen from the hydroperoxy intermediate with aldehyde or hydrogen peroxide, leading to formation of an excited hydroxide intermediate. The third is excited directly on the binding of superoxide anion to the reduced primary emitter.

Acetaldehyde↗
PubMed1992

Weak chemiluminescence of bilirubin and its stimulation by aldehydes.

Bilirubin in an alkaline solution exhibits a weak chemiluminescence (CL) under aerobic conditions. This spontaneous CL was markedly enhanced by the addition of various aldehydes. The fluorescent emission spectrum of bilirubin, excited by weak intensity light at 350 nm, coincided with its CL emission spectrum (peak at 670 nm). CL emission from bilirubin was not quenched by active oxygen scavengers. This suggests that triplet oxygen reacts with bilirubin, and forms an oxygenated intermediate (hydroperoxide) as a primary emitter (oxidative scission of tetrapyrrole bonds in bilirubin is not involved in this CL). The Ehrlich reaction (test for monopyrroles) and hydrolsulphite reaction (test for dipyrroles) on the CL reaction mixture and unreacted bilirubin showed no differences. When the CL was initiated by singlet oxygen, rather than superoxide anion, monopyrrole, was detected in the reaction products by gel chromatography. The inhibitory effect of a scavenger of singlet oxygen on CL was eliminated in the presence of formaldehyde. Therefore, triplet carbonyl, formed by singlet oxygen through the dioxetane structure in bilirubin, is not an emitter. The reaction mechanism of bilirubin CL and the formation of a hydroperoxide intermediate is discussed in relation to the chemical structure of luciferin molecules from bioluminescent organisms.

Acetaldehyde↗
PubMed1992

Bilirubin chemiluminescence induced by the attack of active oxygen species.

Ultraweak chemiluminescence (CL) from bilirubin occurs in the presence of triplet oxygen and is stimulated by the addition of aldehydes. Active oxygen species also enhance bilirubin CL, in the absence of aldehydes. An inhibitory effect of active oxygen scavengers on the CL indicated that active oxygens generated from the decomposition of added hydrogen peroxide or from the xanthine-xanthine oxidase reaction contributed to the CL from bilirubin molecules. However, the contribution of singlet oxygen to the CL disappeared in the presence of formaldehyde. This suggested that the scission of tetrapyrrole bonds via a dioxetane intermediate or the production of triplet carbonyls from the oxidation of aldehydes by singlet oxygen was not involved in the CL, at least in the presence of formaldehyde. The spectrum of CL induced by the generation of active oxygen was the same as that from the aldehyde-enhanced CL reaction. We propose that the formation of a hydroperoxide (and/or hydroxide) bilirubin intermediate, but not a dioxetane, may be involved in the excitation of bilirubin molecules for CL.

Aldehydes↗
PubMed1992

N-methyl-N'-nitro-N-nitrosoguanidine-induced light emission in Chinese hamster cell cultures: correlation with enhancement of chromosomal aberrations.

N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) was found to induce an ultraweak photon emission in cultures of Chinese hamster fibroblasts (CHL). Measurements suggest that the light emission is due to a reaction between MNNG and cellular metabolites. The light emission depended on the concentration of MNNG and was oxygen-dependent, disappearing in a nitrogen atmosphere. Superoxide dismutase (SOD) or sodium azide decreased the emission intensity. The production of chromosomal aberrations in CHL by MNNG was correlated with the light emission intensity and was inhibited in the presence of SOD.

Animals↗
PubMed1992

Low-level chemiluminescence and life span of Drosophila melanogaster.

Spontaneous photon emission (chemiluminescence, CL) as a monitor of free radical evolution in Drosophila melanogaster which had been maintained at 25 or 30 degrees C for 5 days after emergence was measured. When maintained at 30 degrees C the fly CL intensity was stronger than at 25 degrees C. Under the condition of the higher temperature, the fly life span was shorter (mean life span = 29 days at 30 degrees C and 63 days at 25 degrees C), and oxygen consumption (3.7 microliters/mg.h at 25 degrees C, 4.9 microliters/mg.h at 30 degrees C) and the mobility (movement distance = 25 mm/min at 25 degrees C, 700 mm/min at 30 degrees C) increased, together with augmentation of phospholipid hydroperoxide in the fly total lipids. The CL spontaneously emitted from fly homogenate was decreased by the free radical scavengers both in experiments in vivo and in vitro. The hypothesis is proposed that as the oxygen metabolism grows active, the chemiluminescent reactions that involve oxygen-dependent free radical metabolism, including membrane phospholipid hydroperoxidation, contribute to the acceleration of senescence of fly bodies.

Aging↗