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Biomedical subjects

K Suwa

Publications and source records attributed to K Suwa.

At least 19 recordsLinked to original sources

An 8-cM interstitial deletion on 4q21-q22 in DNA from an infant with hepatoblastoma overlaps with a commonly deleted region in adult liver cancers.

We performed molecular analysis of a germline interstitial deletion of chromosome 4 [del(4)(q21.22q23)], which had been observed in a male infant manifesting early-onset hepatoblastoma (HBL). The chromosomal anomaly in this child was associated with a unique congenital syndrome including HBL, atrial septal defect, ventricular septal defect, patent ductus arteriosus, mental retardation, and seizures. However, the patient did not exhibit a megalencephaly typical of 4q21-22 deletions. His HBL was associated with an increasing serum alpha-fetoprotein level and rapid growth. To define the chromosomal deletion at the molecular level in this child, we analyzed his lymphoblasts with fluorescence in situ hybridization, using as probes a panel of BAC/PAC genomic clones containing STS markers covering the 4q12-27 region. The analysis revealed that the affected chromosome had an 8-cM deletion within 4q21-q22, flanked by markers D4S2964 and D4S2966. This microdeletion overlaps with the commonly deleted region at 4q21-q22 that was recently defined in adult hepatocellular carcinomas.

Adult↗

Analyzing the eye movement of dentists during their reading of CT images.

In order to evaluate the eye movements of dentists when they were interpreting radiographs, ten normal computed tomography (CT) images and ten images with pathologic lesions were shown to eight dentists, and the pattern of their eye movement was qualitatively analyzed. Six fixation point parameters were calculated, including the time required to discriminate between normal and pathologic images (X(1)), the total fixation point count (X(2)), the total travel distance between fixation points (X(3)), the average time spent on each fixation point (X(4)), the total gaze fixation time (X(5)), and the maximum gaze fixation time spent on each image (X(6)). When the subjects were interpreting pathologic images, X(2) and X(4) were shorter; however, when they were viewing normal images, time was spent on observing multiple fixation points before the completion of the interpretive process. While pathologic images were recognized through top-down processing, there was a tendency for normal images to be recognized through bottom-up processing. The results of discriminant analysis, using a linear discriminant function, indicated that the independent variables X(2) and X(4) and the dependent variable X(5) were the only variables that contributed significantly to differentiating between normal and pathologic images. The linear discriminant function was Z = 9.0 x 10(-2) x X(2) + 3.0 x X(4) - 2.1 (discriminant score: Z < 0, pathologic image; Z > or = 0, normal image). When the mean value of each individual's gaze fixation data was substituted into the discriminant formula, the hit rate for normal and pathologic images was discriminated at 94% (15 of 16).

Journal Article↗

Effect of combined leukotriene D(4) and thromboxane A(2) receptor antagonist on mediator-controlled resistance in guinea pigs.

The effects of YM158 (3-[(4-tert-butylthiazol-2-yl)methoxy]-5'-[3-(4-chlorobenzenesu lfonyl )propyl]-2'-(1H-tetrazol-5-ylmethoxy)benzanilide monosodium salt monohydrate), a new dual antagonist for leukotriene D(4) and thromboxane A(2) receptors, on antigen-induced increases in airway resistance were investigated in mediator-controlled novel asthmatic models using actively sensitized guinea pigs. While the predominant mediator was thromboxane A(2), complete inhibition of cyclooxygenase induced mediation by cysteinyl-leukotrienes. About 1-mg/kg indomethacin induced a state where both mediators participated equally. YM158 inhibited increases in resistance whether only one or both mediators were involved. When leukotriene D(4) and thromboxane A(2) equally participated, ED(50) values for 4-oxo-8-[4-(4-phenylbutoxy)benzoylamino]-2-(tetrazol-5-yl)-4 H-1-benzo pyran hemihydrate (pranlukast; 3.9 mg/kg) and 7-(3,5,6-trimethyl-1, 4-benzoquinon-2-yl)-7-phenylheptanoic acid (seratrodast; 2.1 mg/kg) were similar to that for YM158 (8.3 mg/kg), although those effects on the corresponding mediator-induced reaction were 10 times stronger than those of YM158. Additionally, the maximum inhibition of YM158 was stronger than those of either single receptor antagonist. In conclusion, YM158 has a potentially greater efficacy in wider types of experimental asthmatic models than single receptor antagonists.

Administration, Oral↗

Correlations of elevated levels of hexacosanoate in erythrocyte membranes with risk factors for atherosclerosis.

We analyzed erythrocyte membrane C26:0 from 504 volunteers by high-performance liquid chromatography. The associations between the elevated levels of erythrocyte membrane C26:0 (0.20 or greater than 0.20%) and sex, obesity (body mass index> or =26.4), smoking (> or =20 cigarettes per day), present illnesses and past diseases were examined with the chi(2) test. The correlations among age and the levels of erythrocyte membrane C26:0, plasma total cholesterol, triglycerides, LDL cholesterol and HDL cholesterol were analyzed using Spearman's correlation coefficient. Moreover, the frequencies of high levels of erythrocyte membrane C26:0 were examined in male and female subjects divided into seven age groups. The elevated levels of erythrocyte membrane C26:0 were significantly more frequent in male subjects than in females, and were closely associated with obesity, smoking, and atherosclerosis-related diseases of present illnesses. The levels of erythrocyte membrane C26:0 were highly correlated with age and the levels of plasma total cholesterol, triglycerides and LDL cholesterol, and inversely with those of HDL cholesterol. The frequency of high levels of erythrocyte membrane C26:0 in male subjects was greater than that in female subjects in all of the seven age groups. Elevated levels of erythrocyte membrane C26:0 may be closely related with atherosclerosis.

Adult↗

Bispectral analysis of the electroencephalogram does not predict responsiveness to verbal command in patients emerging from xenon anaesthesia.

The bispectral index (BIS) is derived empirically from the electroencephalogram database of patients receiving common anaesthetics, but it may not be valid for uncommon agents. Therefore, we investigated how xenon affects the BIS. Nine and 11 patients were anaesthetized with 0.8 of the minimal alveolar concentration (MAC) of isoflurane (0.92%) and xenon (56%), respectively. After the end of operation, these concentrations were decreased in decrements of 0.1 MAC (isoflurane 0.12% or xenon 7%) and each new concentration was maintained for 15 min. This was repeated until the patient first opened her eyes or squeezed the investigator's hand on command. Isoflurane and xenon at 0.8 MAC reduced the BIS to a median of 40 (range 36-53) and 36 (30-61), respectively. With decreasing concentrations of isoflurane, the BIS increased progressively and it reached a median of 96 (90-98) when the patients awoke. In contrast, four patients receiving xenon responded to verbal command while the BIS was below 50 [median 45 (range 41-49)]. The remaining seven patients in the xenon group awoke when their BIS was greater than 80 [median 96 (range 82-98)], but in four of them the BIS was no greater than 50 when the xenon concentration was only 0.1 MAC (7%) higher than that associated with awakening. We conclude that low BIS values (< 50) do not guarantee adequate hypnosis during xenon anaesthesia.

Adult↗

Minimum alveolar concentration-awake of Xenon alone and in combination with isoflurane or sevoflurane.

BACKGROUND: The minimum alveolar concentration (MAC)-awake is a traditional index of hypnotic potency of an inhalational anesthetic. The MAC-awake of xenon, an inert gas with anesthetic properties (MAC = 71%), has not been determined. It is also unknown how xenon interacts with isoflurane or sevoflurane on the MAC-awake. METHODS: In the first part of the study, 90 female patients received xenon, nitrous oxide (N2O), isoflurane, or sevoflurane supplemented with epidural anesthesia (n = 36 for xenon and n = 18 per group for other anesthetics). In the second part, 72 additional patients received either xenon or N2O combined with the 0.5 times MAC-awake concentration of isoflurane or sevoflurane (0.2% and 0.3%, respectively, based on the results of the first part; n = 18 per group). During emergence, the concentration of an assigned anesthetic (xenon or N2O only in the second part) was decreased in 0. 1 MAC decrements every 15 min from 0.8 MAC or from 70% in the case of N2O until the patient followed the command to either open her eyes or to squeeze and release the investigator's hand. The concentration midway between the value permitting the first response to command and that just preventing it was defined as the MAC-awake. RESULTS: The MAC-awake were as follows: xenon, 32.6 +/- 6.1% (mean +/- SD) or 0.46 +/- 0.09 MAC; N2O, 63.3 +/- 7.1% (0.61 +/- 0.07 MAC); isoflurane, 0.40 +/- 0.07% (0.35 +/- 0.06 MAC); and sevoflurane, 0.59 +/- 0.10% (0.35 +/- 0.06 MAC). Addition of the 0.5 MAC-awake concentrations of isoflurane and sevoflurane reduced the MAC-awake of xenon to 0.50 +/- 0.15 and 0.51 +/- 0.16 times its MAC-awake as a sole agent, but that of N2O to the values significantly greater than 0.5 times its MAC-awake as a sole agent (0.68 +/- 0.12 and 0.66 +/- 0.14 times MAC-awake; P < 0.01, analysis of variance and Dunnett's test). CONCLUSIONS: The MAC-awake of xenon is 33% or 0.46 times its MAC. In terms of the MAC-fraction, this is smaller than that for N2O but greater than those for isoflurane and sevoflurane. Unlike N2O, xenon interacts additively with isoflurane and sevoflurane on MAC-awake.

Adult↗

Effect of YM158, a dual lipid mediator antagonist, on immediate and late asthmatic responses, and on airway hyper-responsiveness in guinea pigs.

The effects of lipid mediator antagonists: the LTD4-receptor antagonist pranlukast, the TXA2-receptor antagonist seratrodast, and the novel dual LTD4- and TXA2-receptor antagonist YM158 (3-[(4-tert-butylthiazol-2-yl)methoxy]-5'-[3-(4-chlorobenzenesu lfonyl) propyl]-2'-(1H-tetrazol-5-ylmethoxy)benzanilide monosodium salt monohydrate) were investigated in animals exhibiting immediate asthmatic response (IAR), late asthmatic response (LAR) and airway hyper-responsiveness (AHR). Antigen-induced LAR and AfR are inhibited by orally administered pranlukast (30, 100 mg/kg) and seratrodast (3, 10 mg/kg). YM158 (30 mg/kg), orally administered before or after IAR induction, also inhibited both LAR and AHR. However, while the inhibitory effects of pranlukast and seratrodast on IAR were marginal, the effects of YM158 (3, 10, 30 mg/kg) were dose-dependent, probably due to its multiple sites of action. Additionally, orally administered YM158 (30 mg/kg) inhibited ozone-induced AHR in guinea pigs. Thus, an antagonist that inhibits several lipid mediators might exhibit greater efficacy in treating asthmatic responses than antagonists with a single site of action. Therefore, YM158 shows great promise as a drug that will be able to treat bronchial asthma and related disorders more potently than currently used single-pathway inhibitors.

Acetylcholine↗

In vivo pharmacologic profile of YM158, a new dual antagonist for leukotriene D4 and thromboxane A2 receptors.

The antagonistic activity of oral YM158 (3-[(4-tert-butylthiazol-2-yl)methoxy]-5'-[3-(4-chlorobenzenesu lfonyl)propyl]-2'-(1H-tetrazol-5-ylmethoxy)benzanilide monosodium salt monohydrate), a new dual antagonist for leukotriene (LT) D4 and thromboxane (TX) A2 receptors, was investigated. Oral YM158 caused dose-dependent inhibition of LTD4-induced increases in plasma leakage and LTD4- or U46619-induced increases in airway resistance, with ED50 values of 6.6, 8.6 and 14 mg/kg, respectively. The dose-range of YM158's inhibitions was almost the same for both LTD4 and TXA2 receptors, and repeated oral doses did not affect its efficacy. Furthermore, oral YM158 inhibited antigen-induced bronchoconstriction. Although the potency of pranlukast for LTD4 receptor antagonism (ED50 = 0.34 mg/kg) is greater than that of YM158 (ED50 = 8.6 mg/kg), the doses of both pranlukast and YM158 for significant inhibition of the antigen-evoked airway response were the same, indicating that the TXA2 receptor antagonism of YM158 plays an important role in its anti-asthmatic effects. In conclusion, YM158 promises to be a novel agent for treating bronchial asthma.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Microsatellite alterations in various sarcomas in Japanese patients.

To determine the usefulness of microsatellite analysis in the differential diagnosis of various sarcomas, we investigated microsatellite alterations at 12 microsatellite loci by polymerase chain reaction and electrophoresis in 39 Japanese patients with sarcomas. The sarcomas were: osteosarcoma, Ewing's sarcoma, chondrosarcoma, liposarcoma, leiomyosarcoma, epithelioid leiomyosarcoma, rhabdomyosarcoma, synovial sarcoma, and malignant fibrous histiocytoma. We also examined ten leiomyomas to contrast with leiomyosarcoma. No microsatellite instability (MSI) or loss of heterozygosity (LOH) were found in Ewing's sarcoma, chondrosarcoma, epithelioid leiomyosarcoma, malignant fibrous histiocytoma, and leiomyoma. Only three patients, one each with liposarcoma, leiomyosarcoma, and synovial sarcoma, manifested MSI, whereas, osteosarcoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma, and synovial sarcoma manifested LOH, with an incidence of 43%, 14%, 86%, 20%, and 75%, respectively. Interestingly, three patients showed unusual patterns of LOH, probably due to intratumoral heterogeneity. Kaplan-Meier analysis revealed that LOH on 11p was predictive of poor prognosis in osteosarcoma. The low incidence of MSI indicates that MSI is not necessary for neoplastic transformation in sarcomas. However, the very high incidence of LOH in leiomyosarcoma indicates that microsatellite analysis may serve for the differential diagnosis of leiomyosarcoma versus leiomyoma. Microsatellite analysis may also predict prognosis in osteosarcoma.

Adolescent↗

Acute relapsing encephalopathy mimicking acute necrotizing encephalopathy in a 4-year-old boy.

A 4-year-old boy showed two episodes of encephalitis/encephalopathy involving disturbed consciousness, convulsion, and paresis associated with the elevated levels of protein and myelin basic protein of the cerebrospinal fluid. MRI studies of the brain revealed symmetrical lesions in the brain stem and thalami at the first episode, and additional lesions were found in the cerebellum involving both the gray and white matter in the second episode. The intensities of MRI lesions were low in T I and high in T2. These episodes were followed by an elevation of the anti-viral antibody titers, for influenza A virus during the first episode and for adenovirus during the second. In the second episode, intravenous methylprednisolone therapy resulted in rapid improvement of his neurological signs.

Brain↗

[Artificial graft replacement increases the speed of the pulse wave velocity along the aorta].

We investigated the change in the pulse wave velocity along the aorta after a part of the vessel was replaced by artificial graft in seven patients. Graft-replacement was performed under general or general combined with epidural anesthesia. The velocity measurement was performed in a standard manner before and after the surgical procedure. The replacement by artificial graft consistently increased the pulse wave velocity of which the means +/- SD were 10.4 +/- 2.4 m.s-1 before the surgery, and 13.3 +/- 3.6 m.s-1 after the surgery, amounting a 26.9 per cent increase. The change was statistically significant. The range of this increase was between 8.9% and 45.7%. No changes were observed in various hemodynamic parameters and hematocrits, except the heart rate which increased from 57.4 to 69.1 +/- 9.0 bpm. We conclude that the speed of the pulse wave velocity along the aorta increases markedly by artificial graft replacement. We propose this change is caused by a marked stiffness of the material of the artificial graft. The exact mechanism, however, remains to be elucidated.

Aged↗

Effects of lipid mediator antagonists on predominant mediator-controlled asthmatic reactions in passively sensitized guinea pigs.

The role of cysteinyl leukotrienes (cys-LTs) and thromboxane A(2) (TXA(2)) in guinea pig models of aspects of bronchial asthma was investigated. In a novel antigen (BSA)-induced asthmatic model using passively sensitized guinea pigs, pretreatment with varying doses of indomethacin controlled the ratio of followed lipid mediators, LTC(4)/D(4)/E(4) and TXB(2), in lungs of challenged guinea pigs. The predominant mediator in indomethacin-untreated asthma was TXA(2), and complete inhibition of cyclooxygenase by i.v. injection of 5-mg/kg indomethacin-induced cys-LTs mainly mediated asthmatic response. Furthermore, a 1-mg/kg indomethacin dose induced an asthmatic state where both cys-LTs and TXA(2) equally participated. Either LTD(4) or TXA(2) receptor antagonists given alone inhibited the asthmatic response in conditions where the corresponding mediator plays a predominant role. The combination of LTD(4) and TXA(2) receptor antagonists exhibited significant effects irrespective of the condition used. Under conditions where both mediators equally participate, a combination of both receptor antagonists showed additive inhibition. YM158, a newly synthesized and orally active dual antagonist for LTD(4) and TXA(2) receptors, showed the same antiasthmatic effect as a combinated LTD(4) receptor antagonist and a TXA(2) receptor antagonist mixture. Therefore, broad-acting compounds such as YM158 are expected to have antiasthmatic efficacies in a broader class of asthmatic patients than single-acting drugs.

Administration, Oral↗

Interstitial deletion of the long arm of chromosome 4 [del(4)(q21.22q23)] and a liver tumor.

We report on a boy with proximal interstitial deletion of chromosome 4, del(4)(q21.22q23). The patient was born at term with a low birth weight, flat nasal bridge, micrognathia, wide-spaced nipples, clinodactyly of fifth fingers, overlapping fingers, post-axial polydactyly of the right foot, micropenis, hypospadias, a dermal sinus, and cardiac malformations. He developed psychomotor retardation, seizures, and a liver tumor with an increased serum alpha-fetoprotein level and rapid growth. The patient carried a deletion of chromosome 4 involving the 4q21-q22 region that was reported to form a unique syndrome. The absence of central nervous system overgrowth and the presence of a malignant liver tumor are unique to our patient, compared to others with the 4q21-q22 deletion syndrome. The clinical manifestations and relationship between the liver tumor and chromosomal anomaly are discussed.

Abnormalities, Multiple↗

Clinical and electroencephalographic findings in juvenile type DRPLA.

We present five different types of dentatorubral-pallidoluysian atrophy in one Japanese family. Two siblings and their paternal uncle manifested the juvenile type dentatorubral-pallidoluysian atrophy, the siblings' father had the late-adult type, and another paternal uncle had the early-adult type. Gene analysis confirmed the diagnosis for the proband and her sibling. By following the clinical courses and electroencephalographic changes, we found that the types of epileptic seizures and the electroencephalograms of the juvenile dentatorubral-pallidoluysian atrophy patients changed as the illness progressed. The siblings exhibited different levels of clinical severity despite the similar deoxyribonucleic acid expansion detected in their lymphocytes.

Adolescent↗

Comparison of acceleromyography and electromyography in vecuronium-induced neuromuscular blockade with xenon or sevoflurane anesthesia.

STUDY OBJECTIVES: To compare acceleromyography (AMG) and electromyography (EMG) with xenon or sevoflurane anesthesia during vecuronium-induced neuromuscular blockade. DESIGN: Prospective randomized study. SETTING: University hospital. PATIENTS: 28 ASA physical status I and II adult patients presenting for elective surgery. INTERVENTIONS: Patients received vecuronium for neuromuscular blockade and either xenon (n = 11) or sevoflurane (n = 17) anesthesia. MEASUREMENTS AND MAIN RESULTS: The first twitch depression, which was expressed as a ratio of the first twitch to that obtained before the blocking drug was administered (T1/Tc), was measured simultaneously by AMG and EMG. T1/Tc as measured by AMG consistently demonstrated greater depression than that by EMG during recovery. The limits of agreement were unacceptably wide, suggesting that T1/Tc obtained by AMG is a poor predictor of T1/Tc as measured by EMG. Such relations were not affected by the anesthetic (xenon or sevoflurane) used. CONCLUSION: AMG and EMG-cannot be used interchangeably with either xenon or sevoflurane anesthesia.

Acceleration↗