Search PubMed⌕ Search

Biomedical subjects

H Kasai

Publications and source records attributed to H Kasai.

At least 37 records · Page 2Linked to original sources
PubMed2001

Correlation of genetic etiology with response to beta-adrenergic blockade among symptomatic patients with familial long-QT syndrome.

Mutations in any of the five genes KCNQ1, KCNH2, KCNE1, KCNE2, and SCN5A can be responsible for familial long QT syndrome (LQTS), an arrhythmogenic disorder that entails a high risk of sudden death. beta-Adrenergic blocking agents are the first therapeutic choice, and 80% of patients treated with these agents show symptomatic relief; however the remaining 20% do not respond well. We previously performed a nationwide analysis of familial long QT syndrome (LQTS) in Japan and identified 32 mutations in the KCNQ1 and KCNH2 genes. In the present retrospective study, we found that patients carrying mutations in the KCNQ1 gene responded better to beta-adrenergic blocking agents than those with KCNH2 mutations (12 of 13 vs 1 of 5; P = 0.0077, Fisher's exact test). This is a good example of the power of genetic diagnosis to direct the selection of appropriate therapy for patients with diseases of heterogeneous genetic etiology.

Adolescent↗
PubMed2001

Normal proliferative responses of peripheral blood mononuclear cells to streptococcal preparation OK-432 in patients with pustulosis palmaris et plantaris constitute a distinct feature from the reduced responses observed in those with psoriasis vulgaris, pustular psoriasis, and acrodermatitis continua of Hallopeau.

It was previously reported that peripheral blood mononuclear cells (PBMC) from the patients with psoriasis vulgaris (PV) showed a reduced proliferative response in vitro to the stimulation of a lyophilized preparation of penicillin-treated low virulence Su-strain of Streptococcus pyogenes group 3, OK-432. In this study, at first it was examined whether OK-432 acts as a superantigen. By analyzing the usage of Vbeta T-cell receptor (TCR) of proliferating T cells stimulated with OK-432, it was found that OK-432 stimulated preferentially Vbeta2 TCR-bearing T cells. Next, to find differences in in vitro responses of PBMC among various types of sterile pustular dermatoses such as pustulosis palmaris et plantaris (PPP), acrodermatitis continua of Hallopeau (AC), and generalized pustular psoriasis (GPP), the proliferative responses of PBMC obtained from these patients under the stimulation of OK-432 were compared. When the PBMC was stimulated with interleukin (IL)-2, no significant difference was found in their proliferative responses among those obtained from the patients with these sterile pustular dermatoses, PV or healthy controls. However, like those from PV patients, PBMC from AC and GPP patients showed significantly smaller responses to OK-432 than those from the healthy controls. In contrast, the proliferative responses of PBMC from the patients with PPP to OK-432 was comparable to those from healthy controls. These results, in addition to its unique clinical and histopathological characteristics, suggest that PPP has a different pathogenetic background from that underlying PV, AC, or GPP.

Acrodermatitis↗
PubMed2001

Sequential-replenishment mechanism of exocytosis in pancreatic acini.

Here we report exocytosis of zymogen granules, as examined by multiphoton excitation imaging in intact pancreatic acini. Cholecystokinin induces Ca 2+ oscillations that trigger exocytosis when the cytosolic Ca 2+ concentration exceeds 1 microM. Zymogen granules fused with the plasma membrane maintain their Omega-shaped profile for an average of 220 s and serve as targets for sequential fusion of granules that are located within deeper layers of the cell. This secondary exocytosis occurs as rapidly as the primary exocytosis and accounts for most exocytotic events. Granule-granule fusion does not seem to precede primary exocytosis, indicating that secondary fusion events may require a plasma-membrane factor. This sequential-replenishment mechanism of exocytosis allows the cell to take advantage of a large supply of fusion-ready granules without needing to transport them to the plasma membrane.

Animals↗
PubMed2001

Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons.

Dendritic spines serve as preferential sites of excitatory synaptic connections and are pleomorphic. To address the structure-function relationship of the dendritic spines, we used two-photon uncaging of glutamate to allow mapping of functional glutamate receptors at the level of the single synapse. Our analyses of the spines of CA1 pyramidal neurons reveal that AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptors are abundant (up to 150/spine) in mushroom spines but sparsely distributed in thin spines and filopodia. The latter may be serving as the structural substrates of the silent synapses that have been proposed to play roles in development and plasticity of synaptic transmission. Our data indicate that distribution of functional AMPA receptors is tightly correlated with spine geometry and that receptor activity is independently regulated at the level of single spines.

Animals↗
PubMed2001

Glycyrrhizin enhances interleukin-12 production in peritoneal macrophages.

Interleukin-12 (IL-12) is a monocyte/macrophage-derived cytokine that plays a prominent role in the development of T helper type 1 (Th1) cell-mediated immune responses. Glycyrrhizin (GL), an aqueous extract of liquorice root, used as Chinese medicine, is known to have various immunomodulating activities. In this study, GL showed a dose-dependent priming effect on lipopolysaccharide (LPS)-induced IL-12 p40 and IL-12 p70 (heterodimer of p40 and p35) protein production by peritoneal macrophages (PM). The maximal effect was observed when GL was intraperitoneally administered 12 hr before the PM were harvested and stimulated in vitro with LPS. The increases in IL-12 p70 and p40 protein production were primarily due to up-regulated transcription of IL-12 p35 and p40 messenger RNAs (mRNAs), as demonstrated by RNase protection assay. The augmentation of IL-12 p40 mRNA expression induced by GL pretreatment was associated with increased NF-kappaB activation. Moreover, GL exhibited the same priming effect on IL-12 production in interferon-gamma knockout (IFN-gamma-/-) mice. The production of granulocyte-macrophage colony-stimulating factor (GM-CSF) was not induced at any time point after GL pretreatment. These findings demonstrated the ability of GL to enhance LPS-induced IL-12 production by peritoneal macrophages, and indicated that the priming effect of GL on IL-12 production was independent of both IFN-gamma and GM-CSF.

Animals↗
PubMed2001

Successful prevention of recurrent ventricular fibrillation by intravenous isoproterenol in a patient with Brugada syndrome.

Intravenous administration of isoproterenol restored the ST-segment configuration to nearly normal in the right precordial leads and completely prevented spontaneous VF attacks in a patient with Brugada syndrome. The formation of a Brugada-type ECG has been attributed to the transmural dispersion of repolarization of the right ventricular epicardium and related to modulation of the autonomic nervous system. Our case may provide clues to the pathophysiological mechanism of this syndrome.

Adult↗
PubMed2001

Changes in DNA 8-hydroxyguanine levels, 8-hydroxyguanine repair activity, and hOGG1 and hMTH1 mRNA expression in human lung alveolar epithelial cells induced by crocidolite asbestos.

We examined 8-hydroxyguanine (8-OH-Gua) formation and 8-OH-Gua repair enzyme activity in pulmonary type-II-like epithelial cells to determine whether oxidative stress induced by asbestos plays a role in its carcinogenic mechanism. A549 cells were incubated with crocidolite asbestos at concentrations of 0, 10, 50 and 100 microg/ml over 27 h. We then evaluated 8-OH-Gua formation, 8-OH-Gua repair enzyme activity and gene expression of 8-oxoguanine-DNA glycosylase 1 (hOGG1) and human MUtT homologue (hMTH1). This was done using a high-performance liquid chromatography system equipped with an electrochemical detector, endonuclease nicking assay and reverse transcription polymerase chain reaction, respectively. Crocidolite induced the formation of 8-OH-Gua in DNA at concentrations of 50 and 100 microg/ml. 8-OH-Gua levels increased at 9 h and had declined to near baseline at 27 h, whereas 8-OH-Gua repair enzyme activity peaked at 18 h post-crocidolite exposure. hOGG1 and hMTH1 mRNA levels were also increased by crocidolite exposure. These data suggest that crocidolite asbestos is associated with epithelial cell injury in the process of carcinogenesis through oxidative stress.

Actins↗
PubMed2001

Age-associated increase of 8-hydroxydeoxyguanosine in human colorectal tissue DNA.

To clarify the role of oxidative stress in aging of colorectal tissue, we analyzed the 8-hydroxydeoxyguanosine (8-OH-dG) levels in colorectal biopsy samples from normal tissue of patients with either colorectal cancer (n = 15) or benign colorectal polyps (n = 40). An age-associated increase of 8-OH-dG was observed (p =.002), although the 8-OH-dG levels were not significantly different between the patients with cancer and those with polyps. These results suggest an increased level of 8-OH-dG formation in human colorectal tissue with age.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Life style and urinary 8-hydroxydeoxyguanosine, a marker of oxidative dna damage: effects of exercise, working conditions, meat intake, body mass index, and smoking.

The urinary levels of 8-hydroxydeoxyguanosine (8-OH-dG), a marker of oxidative DNA damage, of 318 healthy men aged 18 - 58 were measured with high resolution by a newly developed automated high-pressure liquid chromatography (HPLC) system coupled to an electrochemical detector (ECD). The mean 8-OH-dG level (mg / g creatinine) was 4.12 +/- 1.73 (SD). An eleven-fold inter-individual variation was observed. The accuracy of the measurement estimated from the recovery of an added 8-OH-dG standard was 90 - 98%. By univariate analysis, it was found that moderate physical exercise (P = 0.0023) and high body mass index (BMI) (P = 0.0032) reduced the 8-OH-dG level, while physical labor (P = 0.0097), smoking (P = 0.032), and low meat intake (less than once / week) (P = 0.041) increased its level. Based on a multi-regression analysis of the log-transformed values, moderate physical exercise (P = 0.0039), high BMI (P = 0.0099), and age (P = 0.021) showed significant reducing effects on the 8-OH-dG level, while low meat intake (P = 0.010), smoking (P = 0.013), and day-night shift work (P = 0.044) increased its level. These results suggest that many types of life-style factors that either generate or scavenge oxygen radicals may affect the level of oxidative DNA damage of each individual.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Psychosocial factors as a potential trigger of oxidative DNA damage in human leukocytes.

Although numerous studies have been carried out on the stress-cancer linkage, the results are still inconclusive. One of the useful, but rarely applied, methods to assess this linkage is to examine the relationship between psychosocial stress and cancer-predisposing genetic alterations simultaneously. We investigated whether various psychosocial factors can be associated with the levels of 8-hydroxydeoxyguanosine (8-OH-dG), a biomarker of cancer-related oxidative DNA damage, in peripheral blood leukocytes in 362 healthy workers (276 males and 86 females). After adjustments for age, body mass index, cigarette smoking, and alcohol use, female subjects showed positive relationships between the amount of 8-OH-dG and the Tension-Anxiety, Depression-Rejection, Anger-Hostility, Fatigue, and Confusion scores of the Profile of Mood States, respectively. The levels of 8-OH-dG also increased reliably in the female subjects who had poor stress-coping behaviors, particularly wishful thinking strategy, in the NIOSH general job stress instrument. There were positive relationships of the 8-OH-dG levels to average working hours, a self-blame coping strategy, and recent loss of a close family member in male subjects. These findings in a nonclinical sample of healthy adults not only provide evidence of a stress-cancer linkage, but also suggest possible sex differences in the mechanisms of stress-related cancer initiation.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Inappropriate discharges from an intravenous implantable cardioverter defibrillator due to T-wave oversensing.

This report describes the clinical management of 2 patients with ventricular fibrillation (VF) who received inappropriate shocks from an implantable cardioverter defibrillator (ICD) due to T-wave oversensing. Cardiac sarcoidosis was confirmed as the underlying heart disease in 1 patient and idiopathic dilated cardiomyopathy in the other. Within 2 months after ICD implantation, both patients received several inappropriate shocks during sinus rhythm. Stored electrograms showed decreased R-wave amplitudes and increased T-wave amplitudes. The ICD sensed both R- and T-waves as ventricular activation, which met the rate criteria for VF treatment. Reprogramming the sensing threshold in association with administration of a drug to slow the heart rate decreased the incidence of the inappropriate shocks in both patients, but these palliative measures did not completely suppress the inappropriate shocks. To avoid T-wave oversensing, the repositioning or adding of a sensing lead is required. The potential risk of T-wave oversensing in ICD patients who have small R-wave amplitudes should be recognized.

Adult↗
PubMed2001

Correlation between the effective refractory period and activation-recovery interval calculated from the intracardiac unipolar electrogram of humans with and without dl-sotalol treatment.

In experimental studies and/or human body surface mapping, the activation-recovery interval (ARI) is used as a parameter to estimate local repolarization. However, it has not been clarified whether the ARI calculated from the intracardiac unipolar electrogram of humans reasonably represents the local effective refractory period (ERP). Measurement of ARIs at multiple ventricular sites can be helpful in assessing the dispersion of ventricular refractoriness of humans, so we examined the relationship between ERP and ARI in the control state and under treatment with dl-sotalol during clinical electrophysiologic studies (EPS). Of 19 patients, an EPS was performed in the control state in 12 and during treatment with dl-sotalol in the other 7. Quadripolar electrode catheters with an interelectrode distance of 5 mm were placed at the right atrium and in the right ventricle. Using atrial pacing, the heart rate was increased incrementally by 10 beats/min, and ERP and ARI were measured for each pacing rate. The ERP at the right ventricle was measured by single extrastimulation between the first and third distal electrodes of the catheter in the right ventricle, and the ARI was calculated from the second distal unipolar electrode of the same catheter as the interval between the minimum derivative of the intrinsic deflection and the maximum derivative of the T wave. In all patients, the unipolar electrogram was stable during the entire EPS, and 83 data points in the control group and 50 in the dl-sotalol group were analyzed. At each pacing rate, the beat-to-beat difference of ARI was less than 10 ms. As the atrial pacing rate increased, the ERP and ARI were progressively shortened, and linear regression analysis revealed an excellent correlation between ERP and ARI. At the same pacing rate, the ERP and ARI in the dl-sotalol group were longer than those in the control group, but no difference was observed in the slope (close to 1.0) and in the intercept of the regression lines between ERP and ARI. In the human ventricle, the ARI calculated from the intracardiac unipolar electrogram represents the local ERP both in the control state and under treatment with dl-sotalol. The ARI can be used as a parameter of local refractoriness and used to study the distribution of refractoriness in the human ventricle.

Adolescent↗
PubMed2001

Inappropriate discharges by fourth generation implantable cardioverter defibrillators in patients with ventricular arrhythmias.

The study prospectively investigated the incidence, cause and efficient management of inappropriate discharge by the fourth generation implantable cardioverter-defibrillator (ICD) system in 45 patients (mean age, 57+/-16 years). During the follow-up period of 27+/-17 months, 18 patients (40%) experienced one or more inappropriate therapies: sinus and supraventricular tachycardia (15 patients) and T wave oversensing (3 patients). In the 15 patients, re-programming of the tachycardia detection interval and/or additional treatment with beta-blocking agents were effective. In the 3 patients with T wave oversensing, the arrythmia was associated with an increase in T wave amplitude, change in T wave morphology and decreased R wave amplitude, and re-programming of the sensitivity of the local electrogram or changing the number of intervals to detect ventricular tachycardia decreased the number of inappropriate discharges in all 3 patients. In conclusion, inappropriate therapies are common problems in patients treated with the fourth generation ICD system, but most of them can be resolved using the dual-chamber ICD system. However, in patients with T-wave oversensing, it is difficult to avoid inappropriate discharge completely, even if the dual-chamber ICD system is implanted.

Adolescent↗
PubMed2001

Sequence specificity of the 8-hydroxyguanine repair activity in rat organs.

The base excision repair system for 8-hydroxyguanine (8-OH-Gua) is believed to play a role in the prevention of mutations, such as GC-to-TA transversion, which leads to cancer development. However, the exact repair mechanism is still unclear. In this study, we examine whether the repair activity level for 8-hydroxyguanine, one of the major forms of oxidative DNA damage, depends on the sequence of the substrate DNA. We prepared six different oligonucleotides containing 8-hydroxyguanine as substrates and reacted them with crude extracts from the livers and kidneys of 8-week-old Sprague-Dawley rats. As a result, up to a 10-fold difference in the repair activity levels was observed, depending on the substrates used. Based on this observation, we suggest that the repair systems may act with sequence specificity on the damaged DNA.

Animals↗
PubMed2001

Three patients with isolated adrenocorticotropin deficiency presenting with neuroleptic malignant syndrome-like symptoms.

We report 3 patients with isolated adrenocorticotropin (ACTH) deficiency presenting with neuroleptic malignant syndrome (NMS)-like symptoms. All patients were in their 60's or 70's and showed consciousness disturbance, a high-grade fever, extrapyramydal signs, and muscle enzyme elevations, which met the criteria for NMS. Also, they all showed hyponatremia induced by isolated ACTH deficiency. In addition to the standard therapy for NMS, corticosteroid supplement therapy was effective in all patients. There thus appear to be subjects with isolated ACTH deficiency among patients presenting with NMS-like symptoms, and adrenal and pituitary function should be checked in NMS patients with hyponatremia.

Adrenocorticotropic Hormone↗
PubMed2001

[Current situation and problems inherent to long-term home medical care as compared with medical care provided in nursing homes].

We compared 18 patients under long-term home medical care and 11 patients who entered a nursing home after receiving home medical care, to analyze the factors thought to influence continuation of home care. There was no statistical difference between the mean age of both groups, but the mean age of main caretakers in the former (mean 59 years old) was lower compared with that of caretakers in the latter (mean 70 years old). There were various reasons for them to enter a nursing home after receiving home care. Five of the 11 patients entered the nursing home after long-term hospitalization in spite of no deterioration in their degree of handicap at discharge. We think the long-term hospitalization may reduce the motivation of caretakers. It is indicated that the age of caretakers and ability, especially motivation to provide care are important factors to continue home medical care.

Aged↗
PubMed2000

Hexamminecobalt(III) chloride inhibits glucose-induced insulin secretion at the exocytotic process.

Hexamminecobalt(III) (HAC) chloride was found to have a potent inhibitory effect on glucose-induced insulin secretion from pancreatic islets. HAC at 2 mm inhibited the secretion in response to 22.2 mm glucose by 90% in mouse islets. Perifusion experiments revealed that the first phase of insulin secretion was severely suppressed and that the second phase of secretion was completely abrogated. Removal of HAC from the perifusate immediately restored insulin secretion with a transient overshooting above the normal level. However, HAC failed to affect glucose-induced changes in d-[6-(14)C]glucose oxidation, levels of reduced forms of NAD and NADP, mitochondrial membrane potential, ATP content, cytosolic calcium concentration, or calcium influx into mitochondria. Furthermore, HAC inhibited 50 mm potassium-stimulated insulin secretion by 77% and 10 microm mastoparan-stimulated insulin secretion in the absence of extracellular Ca(2+) by 80%. The results of a co-immunoprecipitation study of lysates from insulin-secreting betaHC9 cells using anti-syntaxin and anti-vesicle-associated membrane protein antibodies for immunoprecipitation or Western blotting suggested that HAC inhibited disruption of the SNARE complex, which is normally observed upon glucose challenge. These results suggest that the inhibitory effect of HAC on glucose-induced insulin secretion is exerted at a site(s) distal to the elevation of cytosolic [Ca(2+)], possibly in the exocytotic machinery per se; and thus, HAC may serve as a useful tool for dissecting the molecular mechanism of insulin exocytotic processes.

Adenosine Triphosphate↗