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Biomedical subjects

T Ohkubo

Publications and source records attributed to T Ohkubo.

At least 163 records · Page 9Linked to original sources
PubMed1997

Slime formation as a marker of serious infection with methicillin-resistant Staphylococcus aureus.

Strains of methicillin-resistant Staphylococcus aureus (MRSA) are potential pathogens in patients undergoing major surgery and in patients who are immunocompromised. Some MRSA produce a viscous extracellular slime that may interfere with immune function. In this study, slime formation by MRSA was examined in cases of nosocomial infection by this pathogen at a single hospital. The antibacterial resistance, phage and enterotoxin characteristics of strains isolated from patients with fatal infections were determined. MRSA strains were classified as those associated with fatal infection; causing progressive infection; causing superficial infection; and those isolated from the nasal cavity of the health-care professionals as a control group. The incidence of slime formation was highest in the MRSA associated with fatal infection. The incidence of slime formation in the control group was significantly lower than that in the other groups. Results suggest that slime formation by MRSA may be associated with a more severe infection. Rapid identification of slime-forming MRSA may facilitate the initiation of appropriate treatment and improve the patient's prognosis.

Biomarkers↗
PubMed1997

Prediction of wall motion improvement after coronary revascularization in patients with postmyocardial infarction: diagnostic value of dobutamine stress echocardiography and myocardial contrast echocardiography.

The diagnostic value of dobutamine stress echocardiography, myocardial contrast echocardiography and dipyridamole stress thallium-201 single photon emission computed tomography (SPECT) for predicting recovery of wall motion abnormality after revascularization was evaluated in 13 patients with postmyocardial infarction. Seventeen segments showed severe wall motion abnormalities before revascularization. Nine segments which had relatively good Tl uptake on delayed SPECT images despite severely abnormal wall motion were opacified during myocardial contrast echocardiography, and showed improved wall motion after revascularization. In contrast, three segments which had poor Tl uptake and severely abnormal wall motion were not opacified during myocardial contrast echocardiography, and showed no improvement in wall motion during dobutamine stress echocardiography and after revascularization. The following three findings were assumed to be signs of myocardial viability: 1) good Tl uptake on delayed SPECT images; 2) improved wall motion by dobutamine stress echocardiography; and 3) positive opacification of the myocardium by myocardial contrast echocardiography. Myocardial contrast echocardiography had the highest sensitivity (100%) and negative predictive value (100%). Delayed SPECT images had the highest specificity (100%) and positive predictive value (100%). Dobutamine stress echocardiography had a sensitivity of 83.0%, specificity of 80.0%, positive predictive value of 90.9%, and negative predictive value of 66.7%, respectively. Myocardial contrast echocardiography showed the lowest specificity (60.0%). The techniques of dobutamine stress echocardiography and SPECT, though noninvasive, may underestimate wall motion improvement after revascularization. Further examination by myocardial contrast echocardiography is recommended to assess myocardial viability for determining the indications for coronary revascularization in spite of its invasiveness.

Cardiotonic Agents↗
PubMed1997

Hepatectomy of right superior portion (segment VII and VIII) combined with right hepatic vein reconstruction: a case report.

A 63-year-old man was admitted for the surgical treatment of hepatocellular carcinoma in the segment VIII. The tumor was 4 cm in size, and the major trunk of the right hepatic vein and a branch of the middle hepatic vein were compressed by the tumor on preoperative hepatic venogram. To preserve the remnant liver function, resection of segments VII and VIII combined with right hepatic vein reconstruction was attempted. Right hepatic vein was reconstructed using an autologous external iliac vein graft after resection of segments VII and VIII with the reason that the inferior right hepatic vein was small in this case and the congestive change was recognized on the surface of segment V and VI after temporary clamp of the right hepatic vein. The postoperative course was uneventful, and the grafted portion was patent on postoperative hepatic venogram. Postoperative pathological examination revealed that poorly differentiated hepatocellular carcinoma of 4 cm x 3.5 cm in size existed in the segment VIII, and directly infiltrated to the main trunk of the right hepatic vein. This is uncommon operative method, but may be useful for preservation of the remnant liver function.

Carcinoma, Hepatocellular↗
PubMed1996

Liquid chromatographic determination of manidipine in serum with electrochemical detection.

A highly sensitive and selective method for determining a dihydropyridine calcium antagonist, manidipine, by liquid chromatography using column switching with electrochemical detection was developed. Manidipine in serum was extracted by a rapid and simple procedure based on C8 bonded-phase extraction and then silica extraction. Manidipine and nilvadipine as an internal standard were separated on a C8 bonded-phase HPLC column and detected by high conversion efficiency amperometric detection at +0.7 V. Manidipine and nilvadipine (I.S.) were separated from an endogenous interference peak in serum and concentrated on a pre-column (C18) by column switching using an isocratic mobile phase, and then the corresponding fractions were introduced to an analytical column with a C8 stationary phase. Determination of manidipine was possible over the concentration range 0.5-10 ng/ml: the limit of detection was 0.3 ng/ml. The recovery of manidipine added to serum was 93.1-98.4% with coefficients of variation of less than 7.1%. The method is applicable to drug level monitoring in the serum of healthy volunteers treated with manidipine and to the analysis of pharmacokinetics.

Calcium Channel Blockers↗
PubMed1996

Dietary linolenic acid-mediated increase in vascular prostacyclin formation.

To define vascular effects of an enhanced dietary alpha-linolenic acid intake, 28 spontaneously hypertensive rats were fed a 3% sunflowerseed oil (44% linoleic acid) diet; in 3 groups (7 rats each), the diet was supplemented with 1, 2.5 or 5% linseed oil containing 62% alpha-linolenic acid. alpha-Linolenic acid was incorporated up to 12% in the aorta of the 5% linseed oil group. The eicosapentaenoic acid content was not significantly increased. The content of arachidonic acid and docosatetraenoic acid was moderately reduced in rats fed 5% linseed oil. The generation of 6-keto-PGF1 alpha (degradation product of prostacyclin) assessed by HPLC/electrochemical detection was, however, markedly increased (p < 0.05) in rats fed 2.5 and 5% linseed oil. The minor prostanoids TXB2, PGE2 and PGF2 alpha were not significantly altered. The high systolic and diastolic blood pressure of SHR monitored by radio telemetry was more effectively reduced (p < 0.05) in the light, i.e. sleep, cycle. An increased prostacyclin formation and lowered vascular arachidonic acid content associated with enhanced dietary alpha-linolenic acid intake would thus be expected to prove beneficial in the prevention of vascular disorders.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Circadian blood pressure variation related to morbidity and mortality from cerebrovascular and cardiovascular diseases.

The mortality rate of stroke has decreased dramatically over the past 30 years in Japan, but the prevalence of cerebral infarction has increased, mainly because of the higher incidence of nonfatal cerebral infarction in the elderly. Significant advances in the development of antihypertensive drugs over the last 30 years have contributed to the decrease in stroke mortality, but antihypertensive treatment appears to relate to an increase in the prevalence of cerebral infarction in the elderly. We investigated the risks of low BP levels determined by ambulatory BP monitoring and home BP measurements to clarify the previously reported J-shaped relationships between the incidence of ischemic cardiovascular disease and BP levels after treatment. A long-term prospective study of all causes of mortality and cerebrovascular and cardiovascular mortality has been conducted in Ohasama, Japan, since 1987. Cox proportional hazard model after adjusting for age and sex demonstrated that during a 5-year follow-up period involving 893 of the subjects aged 50 years and over in this cohort, those with the lowest quintile of ambulatory BP levels exhibited a significantly high hazard ratio of cardiovascular as well as all causes of mortality. During the same follow-up period in 1,226 subjects aged 50 years and over, those with the lowest and highest quintiles of home BP levels demonstrated a significantly high hazard ratio of cardiovascular as well as all causes of mortality (i.e., J-shaped relationship). The amplitude of the fall in nocturnal BP obtained by ambulatory BP monitoring correlated positively with the severity of silent cerebrovascular lesions in elderly women, but not in elderly men. These results suggest the significantly high risk associated with low BP levels, which can be determined only by ambulatory and home BP measurements, but not by casual BP measurements.

Age Factors↗
PubMed1996

Evaluation of myocardial ischemia and infarction by signal-averaged electrocardiographic late potentials in children with Kawasaki disease.

We investigated myocardial ischemia and old myocardial infarction noninvasively using signal-averaged electrocardiographic late potentials (LPs) in patients with Kawasaki disease. Patients were divided into 4 groups: a noncoronary artery lesion group (n=136), a coronary artery lesion group (without myocardial ischemia and an old myocardial infarction; n=33), an ischemia group (n=16), and an old myocardial infarction group (n=13). Grouping was based on exercise thallium-201 myocardial scintigraphy, thallium-201 myocardial scintigraphy, exercise electrocardiography, coronary angiography, left ventriculography, and echocardiography. Signal-averaged electrocardiograms were recorded using a high-resolution system. Values of filtered QRS duration (f-QRSd), root-mean-square voltage, and duration of low-amplitude signal were judged using our own body surface area-related criteria (n=205) to determine positive rates of LPs and sensitivities and specificities to ischemia and infarction. These data were also interpreted using published criteria for adults and compared with those interpreted by our criteria. Positive rates by our criteria were 0% in the noncoronary artery lesion group, 9.1% in the coronary lesion group, 56.3% in the ischemia group, and 69.2% in the old myocardial infarction group. However, using the criteria for adults, these values were 0%, 3.0%, 25%, and 46.2%, respectively. Sensitivities to ischemia and infarction using our criteria were significantly higher (56.3% and 69.2%) than those using the criteria for adults (p < 0.05). Moreover, specificities to ischemia and infarction were very high (93.4% and 93.5%, respectively) using our criteria, and there were no significant differences from specificities using the criteria for adults. Also, we examined the reproducibility of values of LPs and LP parameters. The values of filtered QRS duration showed a high reproducibility in both LP-positive and -negative groups, followed by low-amplitude signal and then root-mean-square voltage. The results of LP presence or absence showed 100% reproducibility for both the LP-positive and -negative groups, supporting the utility of LPs for clinical applications. Thus, LPs provide useful information in a noninvasive manner for clarifying ischemia and infarction in patients with Kawasaki disease.

Action Potentials↗
PubMed1996

Solution Strucutres of DNA duplexes containing a DNA x RNA hybrid region, d(GG)r(AGAU)d(GAC) x d(GTCATCTCC) and d(GGAGA)r(UGAC) x d(GTCATCTCC).

The solution structures of two DNA duplexes containing a DNA*RNA hybrid region at different sites, d(GG)r(AGAU)d(GAC) x d(GTCATCTCC) (DHD, where D and H represent the DNA and DNA x RNA hybrid segments, respectively) and d(GGAGA)r(UGAC) x d(GTCATCTCC) (DDH), were determined by nuclear magnetic resonance spectroscopy to clarify the structural features of the D-H and H-D junctions. All proton-proton distances were derived from the NOESY spectra, with mixing times of 45 ms, and the restrained molecular dynamics were carried out starting from the typical A- and B-form conformations. Both duplexes were converged from the respective initial structures into structures with RMSD values of less than 1.0 angstrom. These structures were subjected to full relaxation matrix refinement to produce the final structures. In the case of the D-H junction, where the ribonucleotide was linked to the 3'-end of the DNA, the H2' and H2" signals of the deoxynucleotide overlapped completely, and the ribonucleotide had a H1'-H2' coupling constant larger than that of the normal C3'-endo sugar pucker. The dihedral angles, the pseudorotation phase angles, and the helical parameters changed at the H-D junction, but not at the D-H junction. A detailed comparison of the two duplexes revealed the structural heterogeneity between the DNA segment and the DNA x RNA hybrid region and the transitions at the junctions.

Base Sequence↗
PubMed1996

Simple and selective assay of 4-hydroxymephenytoin in human urine using solid-phase extraction and high-performance liquid chromatography with electrochemical detection and its preliminary application to phenotyping test.

A simple and selective HPLC method for the determination of 4-hydroxymephenytoin (4-OH-M) in human urine, using a controlled potential coulometric detector equipped with a dual working electrode cell of fully porous graphite, has been developed. After acid hydrolysis of urine, 4-OH-M and the internal standard (I.S.), 5-hydroxy-1-tetralone, were extracted from urine by means of a Bond Elut Certify LRC column. The extracts were chromatographed on a reversed-phase mu Bondapak C18 column using methanol-50 mM KH2PO4 (pH 4.0) (30:70, v/v) as the mobile phase at a flow-rate of 1.0 ml/min. Electrochemical detection at applied potential of 800 mV resulted in a limit of quantitation of 0.76 micrograms/ml. The method showed a satisfactory sensitivity, precision, accuracy, recovery and selectivity. The present method was applied to the phenotyping test in thirteen Japanese healthy volunteers who received an oral 100-mg racemic mephenytoin. The phenotypes determined by the present method were found to be in agreement with those obtained with the reported customary assay based on gas chromatography.

Adult↗
PubMed1996

The defective secretion of a naturally occurring alpha-1-antichymotrypsin variant with a frameshift mutation.

A newly found variant alpha-1-antichymotrypsin (ACT), ACT Isehara-2, has a deletion of two bases (AA) at codon 391 near the carboxyl terminus. This frameshift mutation caused a change in the amino acid sequence and generated 10 extra amino acids (408 amino acids total) [Tsuda, M., Sei, Y., Matsumoto, M., Kamiguchi, H., Yamamoto, Y., Shinohara, Y., Igarashi, T. & Yamamura, M. (1992) Hum. Genet. 91. 467-468]. The serum ACT levels in three unrelated heterozygotes with this mutant ACT gene were 37% 49% and 54% that of the normal individuals. To examine the reduced serum levels, the normal ACT and the mutant ACT created by site-directed mutagenesis were transfected into COS-7 cells for comparison. The value for the retention rate (intracellular ACT/total ACT) was apparently higher in the cells expressing mutant ACT Isehara-2 than those bearing the normal gene. In the pulse-chase experiments, the secretion of the synthesized mutant ACT into the medium was not observed, whereas the normal ACT was mostly secreted as a 64-kDa form. The endoglycosidase H digestion and an electron microscopic analysis indicated that the retained mutant ACT was present in the endoplasmic reticulum. These results provide the biochemical basis for the decreased serum ACT level of individuals with ACT Isehara-2, and suggest the importance of the carboxyl-terminal region for its secretion.

Amino Acid Sequence↗
PubMed1996

A new type of major aminopeptidase in bovine brain.

A new type of major aminopeptidase was purified from bovine brain by ammonium sulfate fractionation and TMAE-fractogel (anion exchange), arginine-Sepharose 4B, Sephadex G-150, and Sephadex G-100 column chromatography. The purified enzyme showed a maximum activity at pH 7.2, and its molecular size was estimated to be 98,000 by gel filtration and 104,000 by SDS-PAGE with or without 2-mercaptoethanol. Further properties were activation by thiol reagents; inhibition by EDTA, puromycin, bestatin, amastatin, actinonin, leuhistin and probestin; and very low concentrations of Cu2+, Cd2+, Pb2+, Al3+, Fe3+, and Zn2+ inhibited activity. The enzyme hydrolyzed several amino acyl-7-amido-4-methylcoumalin derivatives (amino acid-MCA). The order of MCA-substrate specificity expressed as kcat/Km is Lys-MCA > Arg-MCA > Leu-MCA > Met-MCA > Phe-MCA > Tyr-MCA > Ala-MCA >> Gly-MCA, Pro-MCA, Ser-MCA, Asn-MCA. Immunoreactivity of the antibody against the purified aminopeptidase was observed in human brain and most rat tissues examined including brain, liver, kidney, lung, heart, and skeletal muscle at the same molecular size as in bovine brain aminopeptidase. Most of the Lys-, Leu-, Met-, and Phe-MCA degrading activity in crude bovine and human brain extracts was absorbed by the aminopeptidase IgG, suggesting that this aminopeptidase is a major enzyme, sharing at least Lys-, Leu-, Met-, and Phe-MCA degrading aminopeptidase activities in the brains.

Amino Acids↗
PubMed1996

Influence of recombinant chicken prolactin on thyroid hormone metabolism in the chick embryo.

The influence of a recombinant chicken prolactin (rcPRL) preparation on thyroid function was studied in 18- and 19-day-old chicken embryos. Displacement studies on hepatic microsomes indicate that this preparation does not compete with radiolabeled chicken growth hormone (cGH) for hepatic GH-receptor binding. In a first series of experiments rcPRL or immunoaffinity-purified cGH was injected intravenously in 19-day-old chicken embryos. After 2 hr, cGH increased plasma T3 in a dose-dependent way by inhibiting hepatic inner ring type III deiodination (IRD-III) and consequently T3 degradation. Outer ring deiodination (ORD-I) was not influenced confirming previous results. The rcPRL preparation (2 and 10 microg) did not influence plasma T3, but depressed T4 and raised hepatic IRD-III activity simultaneously, whereas no influence on hepatic ORD-I activity could be found. In a second experiment on 18-day-old embryos, it could be demonstrated that the effect of 2.5 microg cGH on plasma T3 and liver IRD-III lasted up to 6 hr after injection, whereas 2.5 microg cPRL affected plasma T4 and liver IRD-III up to 2 hr. Both rcPRL and cGH depressed rT3 up to 6 hr, whereas an injection of rcPRL, but not of cGH, elevated plasma concentrations of corticosterone. These results indicate that prolactin may have a role, together with GH, in controlling peripheral thyroid hormone metabolism.

Animals↗
PubMed1996

A kinetic and dynamic study of oral alprazolam with and without erythromycin in humans: in vivo evidence for the involvement of CYP3A4 in alprazolam metabolism.

OBJECTIVE: To assess the possible involvement of CYP3A4 in the metabolism of alprazolam in vivo. METHOD: Twelve healthy male volunteers were randomly allocated to one of the two different treatment sequences, placebo-erythromycin or erythromycin-placebo, with an at least 6-week washout period between the two trial phases. Each volunteer received 400 mg erythromycin or matched placebo given orally three times a day for 10 days and an oral dose (0.8 mg) of alprazolam on the posttreatment day 8. Plasma concentration of alprazolam was measured up to 48 hours after the administration, and psychomotor function was assessed at each time of blood samplings with use of the Digit Symbol Substitution Test, visual analog scale, and Udvalg for kliniske undersøgelser side effect rating scale. RESULTS: Erythromycin significantly (p < 0.001) increased the area under the plasma concentration-time curves (200 +/- 43 versus 322 +/- 49 ng . hr/ml from 0 to 48 hours and 229 +/- 52 versus 566 +/- 161 ng . hr/ml from 0 hour to infinity), decreased the apparent oral clearance (1.02 +/- 0.31 versus 0.41 +/- 0.12 ml/min/kg), and prolonged the elimination half-life (16.0 +/- 4.5 versus 40.3 +/- 14.4 hours) of alprazolam. However, any psychomotor function variables did not differ significantly between the erythromycin and placebo trial phases. CONCLUSION: This study suggests that erythromycin, an inhibitor of CYP3A4, inhibits the metabolism of alprazolam, providing an in vivo evidence for the involvement of CYP3A4 in its metabolism. However, the kinetic change of alprazolam by erythromycin does not result in the pharmacodynamic change of this triazolobenzodiazepine, at least after single dosing.

Administration, Oral↗
PubMed1996

Seasonal variation in blood pressure in normotensive women studied by home measurements.

1. The factors influencing the seasonal variation in blood pressure measured at home in normotensive women were examined. 2. Sixteen female subjects (56.3 +/- 7.9 years old, mean +/- SD) measured their blood pressure and pulse rate at home each morning for more than 20 times per month for at least 1.5 years. Blood pressure and body weight were also determined in the office once or twice a month in that period. Monthly means of outdoor and indoor temperatures and daytime length were obtained from the Meteorological Observatory. The single cosinor method was used to evaluate circannual rhythm. 3. We observed a biphasic seasonal variation in self-recorded blood pressure measured at home, environmental temperature and daytime length but found no apparent seasonal variation in body weight and blood pressure measured in the office. The lowest levels of systolic and diastolic blood pressure measured at home were observed in July. The longest daytime length was recorded in June, while the highest outdoor temperature and indoor temperature were recorded in August, indicating that the longest daytime length preceded and the highest environmental temperature lagged behind the lowest level of blood pressure. The shortest daytime length is in December. The lowest outdoor and indoor temperature were observed in January, while the highest levels of self-recorded systolic blood pressure and diastolic blood pressure were in January and December, respectively. Half-amplitudes of self-recorded systolic and diastolic blood pressure were 2.6 +/- 1.0 mmHg and 2.0 +/- 0.8 mmHg, respectively. 4. These findings indicate the importance of a seasonal effect, i.e. daytime length and the environmental temperature, on the blood pressure of individuals.

Adult↗
PubMed1996

Implications of the zinc-finger motif found in the DNA-binding domain of the human XPA protein.

BACKGROUND: The XPA (xeroderma pigmentosum group A) protein specifically recognizes the UV-or chemically damaged DNA lesions, and triggers the nucleotide excision repair process. This XPA protein contains the functional domain which is crucial to the recognition of damaged DNA. Its primary structure suggests that this DNA binding domain may contain a zinc-finger motif. To gain a more detailed insight into this zinc-finger motif, we have measured the 113Cd-NMR spectra of the DNA binding domains derived from the wild-type and mutant XPA proteins. RESULTS: 113Cd-NMR analysis, combined with atomic absorption and site-directed mutagenesis, revealed that the DNA binding domain contains one zinc ion, coordinated with four cysteine residues (Cys105, Cys108, Cys126, and Cys129), that is essential for correct protein folding in vivo and in vitro. CONCLUSIONS: The four ligand cysteine residues form a Cys-X2-Cys-X17-Cys-X2-Cys motif, which is reminiscent of the (Cys)4 type zinc-finger motif found in numerous transcriptional regulatory proteins. However, the secondary structure prediction and the 3D-1D compatibility analysis demonstrate that there is no structural similarity in the vicinity of the zinc-finger motif between the XPA protein and other zinc-finger containing proteins. We conclude that the XPA protein contains a new type of zinc-finger motif.

Amino Acid Sequence↗
PubMed1996

Use of whole-body imaging using Tc-99m RBC in patients with soft-tissue vascular lesions.

We investigated the usefulness of whole-body imaging as an adjunct to spot imaging in soft-tissue vascular lesions, such as hemangiomas and vascular malformations. Spot imaging of the known lesion and whole-body imaging were performed 1-3 hours after the injection of Tc-99m RBC in 42 patients with soft-tissue vascular lesions. Whole-body imaging was considered to be useful in only two patients, who had multiple distant occult lesions in addition to large known lesions. It was suggested that the routine addition of whole-body imaging is not cost effective in patients with soft-tissue vascular lesions, although it may be beneficial for detecting occult lesions in patients with hemangiomas.

Adolescent↗