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Biomedical subjects

H Inaba

Publications and source records attributed to H Inaba.

At least 55 records · Page 3Linked to original sources

Development and applications of new technology for two-dimensional space-time characterization and correlation analysis of ultraweak biophoton information.

We describe the spatial distribution and temporal correlation analysis of ultraweak biophoton emission based on photoelectron pulse time series and position measurement techniques. Experimental results on the spatio-temporal variation of biophoton emission from soybean seedlings after physical and chemical stimulation to the root tip are analyzed. Our results suggest the potential usefulness of this technique to quantify the transmission mechanisms of biological signals in the living system by measuring the biophoton emission.

Photons

Factor VIII gene inversions in severe hemophilia A: results of an international consortium study.

Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells were observed among 225 cases (approximately 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).

Blotting, Southern

Improved detection of medically important fungi by immunoperoxidase staining with polyclonal antibodies.

This study was performed to identify pathological fungi of eight species [Aspergillus fumigatus, Candida albicans, Torulopsis (Candida) glabrata, Cryptococcus neoformans, Fusarium anthophilum, Rhizopus oryzae, Sporothrix schenckii and Trichosporon beigelii] in formalin-fixed, paraffin-embedded tissue sections by indirect immunoperoxidase staining. Mature albino rabbits were immunized with formalin-killed organisms. Antibodies were prepared by precipitation. Immunoperoxidase staining was applied to the paraffin-embedded tissue sections of experimentally infected mice and human autopsy and surgical specimens. Although the cell walls of each fungus stained clearly, many cross-reactivities appeared. However, it was possible to obtain specificity for the eight species by absorption and dilution of the antisera.

Animals

Ultraweak biophoton emission imaging of transplanted bladder cancer.

Biophoton emission or spontaneous ultraweak light emission has been observed from almost all living organisms, with intensities ranging from 10(-19) to 10(-16) W/cm2. The measurement of biophoton emission offers the attractive possibility of noninvasive monitoring of the underlying physiological function of a living system. In the present study, ultraweak biophoton emission from mice with transplanted bladder cancer was detected by a two-dimensional photon-counting system. Photon counts were observed to be 1.51-4.73 times higher from the regions of untreated tumor than from normal regions. Our study suggests that this novel technique may be applicable to the diagnosis of superficial tumors.

Animals

HLA-DRB1*1502 allele, subtype of DR15, is associated with susceptibility to ulcerative colitis and its progression.

HLA-DRB1 allele typing was performed by the PCR-RFLP method on 59 ulcerative colitis (UC) patients and 136 healthy controls. Phenotypic frequencies of HLA-B52 and DR2 were significantly increased among the UC patients, serologically. DNA typing of HLA-DRB1 revealed that the genotypic frequency of DRB1*1502 was higher in UC than in the controls (49.2% vs 17.6%; P < 0.0001). In the analysis of clinical parameters, 82.8% of patients bearing DRB1*1502 were treated with corticosteroids. DRB1*1501 and DRB1*1502 differ in only one amino acid at residue 86 (valine vs glycine), and 66% of the UC patients carried two glycines at position 86 in the HLA-DR beta-chain (vs 51% of control; P < 0.05). These observations suggest that the presence of Gly-86 in the HLA beta-chain and surrounding amino acid sequence of HLA-DRB1*1502 is strongly associated with susceptibility to UC.

Adolescent

Detection of superoxide free radicals in rats with acute pancreatitis.

To study the importance of oxygen-derived free radicals in acute pancreatitis, an experimental study of in vivo detection of superoxide free radicals (O2-) was performed using rats. Using a new chemiluminescence probe (2-methyl-6-[p-methoxyphenyl]-3,7-dihydro-imidazol[1,2-1]pyrazin- 3-one; MCLA; a Cypridina luciferin analogue) and a highly sensitive photon counting system, O2- from the pancreatic surface of rats with experimental acute pancreatitis induced by 180 micrograms cerulein/kg was detected. The time course of MCLA-dependent luminescence suggested that O2- production began 2-3 h after cerulein injection and then decreased gradually. Superoxide free radical production in the pancreas of rats with cerulein-induced acute pancreatitis was confirmed using MCLA-dependent chemiluminescence. This new method allows direct observation of the behavior of oxygen-derived free radicals.

Acute Disease

Inhibition of pulmonary hypertensive response after antigen challenge.

By adding antigen cells into perfusate circulation, a great increase in pulmonary arterial pressure was observed in isolated perfused lung from rabbits previously immunized with human O-N type erythrocytes. To investigate whether thromboxane A2 is the main mediator in pulmonary vasoconstrictive response, we injected antigen erythrocytes into the reservoir after administration of putative inhibition as follows: indomethacin (5 mg/kg, thromboxane A2 synthetase inhibitor), KT2-962 (.1 mg/kg, thromboxane receptor blocker), and pyrilamine (.1 mumol, H1 blocker). Pulmonary vasoconstrictive response after antigen challenge was significantly blocked by both indomethacin and KT2-962, but not by H1 blocker. Although the H1 blocker, pyrilamine, did not significantly block the pulmonary vasoconstrictive response, it did significantly block the bronchoconstrictive response after antigen challenge; however, the bronchoconstrictive response was not blocked by either indomethacin or KT2-962. We conclude that thromboxane is the main mediator in the pulmonary vasoconstrictive response, and histamine is the main mediator in the bronchoconstrictive response.

Animals

Anti-HLA antibody screening with extracted platelet HLA antigens by the mixed passive hemagglutination method.

For the detection of anti-HLA antibody in the serum of patients receiving frequent platelet transfusions, we developed a new method in which platelet antigens are extracted into physiological saline containing 3% sucrose and coated as a layer on a U-type Terasaki plate. In the present study, screening of anti-HLA antibodies was conducted with this plate by the mixed passive hemagglutination test although the plate contained both HLA and HPA. The reactivity determined by this method correlated well with antihuman immunoglobulin-lymphocyte cytotoxicity test (AHG-LCT) results (r = 0.963). The plate can be preserved for at least 2 years at -80 degrees C and is easier to handle than the frozen lymphocyte panels used in the LCT test in which lymphocytes must be kept alive. This new method is an alternative way to screen HLA antibodies. In addition, it is expected that this method will be used to screen anti-HPA antibodies.

Blood Platelets

Modulation of protein kinase C produces glucose-dependent alterations in hemodynamics and metabolism in the perfused liver in fasted rats.

Protein kinase C (PKC) has been suggested to be involved in the regulation of hepatic blood flow and metabolism. To confirm the role of PKC, we studied the effects of active and inactive PKC modulators on hemodynamics and metabolism in the perfused rat liver. In addition, the influence of glucose concentration in the medium was studied. The liver was isolated from fasted Sprague-Dawley rats and perfused through the portal vein at a constant pressure of 12 cm H2O. 4 alpha-Phorbol 12,13-didecanoate, an inactive phorbol ester for PKC, slightly decreased hepatic flow only when its initial concentration was raised to 20 microM. In contrast, 4 beta-phorbol 12,13-didecanoate, an active phorbol ester for PKC, at initial concentrations of 80 nM to 1.28 microM decreased hepatic flow and oxygen consumption in a dose-dependent manner, and increased lactate production. HA-1004, a relatively inactive PKC inhibitor, at an initial concentration of 33 microM did not modify the effects of phorbol 12-myristate 13-acetate (PMA), a potent PKC activator. However, H-7, a relatively specific PKC inhibitor, at a concentration of 33 microM attenuated the effects of PMA. The effects of PMA were enhanced by an increase in n-glucose concentration from 10 to 25 mM but not by an increase in L-glucose concentration. These results suggest that modulation of PKC exerts glucose-dependent influences on hepatic flow and metabolism.

Animals

[Kindling of the rat pyriform cortex in the process of aging].

The author investigated seizure susceptibility in 10-12-month-old male sprague-Dawley rats (elderly group) by kindling of the pyriform cortex (PC). Male rats (3-4 mo.) of the same strain were used as the control group. The kindling development of the elderly group was significantly slower than that of the control group because stages 1 and 2, which are indicative of partial seizures, were prolonged. The incidence of regression of seizure stage during the kindling process was higher in the elderly group than in the control group (70% and 40%, respectively), but not significantly. In addition, the elderly group showed a shorter duration of afterdischarges (AD) through the kindling process, and afterdischarge threshold in the PC was slightly elevated in the elderly group as compared with the control group, but not significantly. There were no significant differences between the two groups in the incidence of falling, and in the latency for falling at the first stage 5 seizure (generalized convulsion). The results indicate that the elderly group has difficulty in acquisition of epileptogenesis, while there is no apparent change in the susceptibility to generalized convulsion as compared with the control group.

Aging

Phase I study of E1077, a novel parenteral cephem antibiotic.

The safety and pharmacokinetics of E1077, a new injectable cephem antibiotic, were evaluated in healthy male adult volunteers. In the single-dose studies, 100, 250, 500, 1,000, and 2,000 mg of E1077 were administered by intravenous infusion at a constant rate for 60 minutes, then 1,000 mg of the drug by intravenous infusion at a constant rate for 5 minutes. The Cmax were 6.4, 15.7 +/- 12.0, 34.7 +/- 4.6, 63.2 +/- 4.6, 142.7 +/- 5.6, and 131.6 +/- 36.0 (means +/- SD) micrograms/mL, respectively, and the Cmax and AUC increased linearly with the dose. Plasma concentration-time curves were well described by a two-compartment open model. The plasma elimination half life of the drug was 1.88 +/- 0.15 hours. The mean urinary recovery within the first 24 hours was 94.1 +/- 5.1% of the dose. In the multiple-dose study, 2,000 mg of E1077 was intravenously administered at a constant rate over 60 minutes every 12 hours for 4.5 days (a total of nine times). The Cmax after the first and ninth doses were 134.0 +/- 17.4 and 135.5 +/- 15.5 micrograms/mL, respectively, and trough levels in day 1 and day 5 (at 12 hours after the first and ninth administration, respectively) were 2.2 +/- 0.8 and 1.9 +/- 0.4 micrograms/mL, respectively. No accumulation of the drug in plasma was observed. There were no significant differences in plasma levels or in the urinary recoveries between the single- and multiple-dose regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Pharmacokinetic and pharmacodynamic profiles of CS-518, a selective, long-lasting thromboxane synthase inhibitor, after single and multiple oral administration to healthy volunteers.

A selective thromboxane (TX) synthase inhibitor, CS-518, was orally administered to healthy male Japanese volunteers and the pharmacokinetic and pharmacodynamic properties were investigated. The time profile of drug concentrations in plasma was determined, and the effects of the drug on platelet aggregation in plasma induced by arachidonic acid (AA) and adenosine diphosphate (ADP) ex vivo were examined. The production of TXB2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in serum during whole blood coagulation ex vivo also were examined. In the single-dose study (50, 100, and 200 mg), plasma concentrations of the drug were well fitted to a one-compartment open model with first-order absorption. The area under plasma concentration curve (AUC) and maximum plasma concentration (Cmax) showed dose-related increases, whereas the mean elimination half-lives remained rather constant (.68-.92 hour). The drug was recovered in urine by 32 to 37% and 62 to 65% as unchanged and conjugated forms (acylglucuronide), respectively, showing almost complete absorption of CS-518. The effect of food intake on the pharmacokinetics of CS-518 was determined at the dose of 100 mg. The time to reach Cmax was prolonged from .42 to 2.08 hours and the Cmax was decreased by about 66%, whereas the AUC and urinary recovery showed no significant changes. The platelet aggregation in plasma induced by AA was markedly inhibited, whereas the secondary aggregation induced by ADP was inhibited to a much less degree. Platelet aggregation by AA was almost completely inhibited 2 hours after administration of any dose and the duration for maintaining the significant inhibition tended to depend on the dose ranging from 48 to 72 hours after administration, which was much longer than expected from the plasma concentration of drug.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha

Suppression by methylprednisolone of augmented plasma endotoxin-like activity and interleukin-6 during cardiopulmonary bypass.

It has been reported that plasma endotoxin, measured by Limulus amoebocyte lysate assays, markedly increased during extracorporeal circulation (ECC). Therefore, this study was undertaken to see if pretreatment with methylprednisolone 30 mg kg-1 modifies the endotoxaemia and associated increases in plasma cytokines in 17 patients undergoing cardiac surgery requiring ECC. We found that methylprednisolone suppressed significantly the ECC-induced increases in plasma endotoxin, measured by a conventional Limulus amoebocyte lysate assay (Toxicolor), and interleukin-6. Plasma concentrations of endotoxin, measured by a highly specific chromogenic Limulus test (Endospecy test), tumour necrosis factor-alpha and interleukin-1 beta did not increase significantly in either the control or methylprednisolone groups.

Adult

Isoflurane modulates phorbol myristate acetate-, prostaglandin D2-, and prostaglandin E2-induced alterations in hepatic flow and metabolism in the perfused liver in fasted rats.

Protein kinase C (PKC) is thought to play an important role in the regulation of hepatic flow and metabolism in the liver. The activation of PKC has been implicated in pathologic responses of the organisms to immunologically active substances including endotoxin. The effects of volatile anesthetics on the hemodynamic and metabolic alterations associated with PKC activation were studied using isolated liver perfusion. The liver was isolated from overnight-fasted, male Sprague-Dawley rats, and placed in a recirculating perfusion-aeration system. The liver was perfused through the portal vein at a constant pressure of 12 cm H2O. Isoflurane at a concentration of 3% maintained hepatic flow, reduced oxygen consumption, and transiently enhanced lactate production. Phorbol 12-myristate 13-acetate (PMA), a potent activator of PKC, at an initial concentration of 80 nM decreased hepatic flow and oxygen consumption, and enhanced lactate production. Isoflurane significantly attenuated the PMA-induced alterations in hepatic flow, oxygen consumption, and lactate production. A similar inhibition of the PMA-induced alterations was observed in the liver treated with halothane at 2%. Isoflurane attenuated the flow reduction and stabilized the oxygen consumption after the administration of prostaglandin D2 (PGD2) and E2 (PGE2), possible mediators of PMA. Isoflurane, and presumably other volatile anesthetics, may elicit beneficial effects on the liver by attenuating the PKC-mediated alterations in hepatic hemodynamics and metabolism when PKC in the liver is activated through pathologic mechanisms.

Animals

Syalil-SSEA1(SLX) levels in supernatant of cultured human lung carcinoma cell lines.

SLX levels in the culture supernatant of the following 50 cell lines were measured by RIA: pulmonary carcinoma cell lines derived from 46 patients, cell lines of other human cancers derived from 4 patients, and 2 passaged human fibroblast cells as control. Of the 46 pulmonary carcinoma cell lines, 17 (37%) were SLX positive. When the SLX-positive rate was analyzed in relation to the histological type of pulmonary carcinoma, the positive rate was 71% (10/14) for adenocarcinoma, 27% (3/11) for squamous cell carcinoma, 33% (2/6) for large cell carcinoma, 0% (0/11) for small cell carcinoma and 50% (2/4) for adenosquamous cell carcinoma. Analysis of the relationship between tumor cell proliferation and SLX level in 20 patients revealed that the SLX level in the supernatant of SLX-producing cell lines becomes higher in proportion to the increase in the number of these cells. The SLX-positive rate did not differ significantly among different stages of pulmonary carcinoma at the time of tissue collection. There was no significant correlation between SLX production and prognosis. SLX production by each cell line was not correlated with the doubling time of the same cell line in vitro or in vivo (in nude mice). SLX production also showed no correlation with the duration of tumor cell passage.

Adult