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Biomedical subjects

Kenji Kuroda

Publications and source records attributed to Kenji Kuroda.

At least 19 recordsLinked to original sources

The relationship between aortic augmentation index and pulse wave velocity: an invasive study.

OBJECTIVES: The aortic augmentation index (AI) and aortic pulse wave velocity (PWV) are known to be indicators of arterial stiffness. However, it is not clear whether aortic AI and PWV reflect aortic stiffness in similar ways. We investigated the relationship between aortic AI and PWV by measuring them directly using a catheter technique. DESIGN AND METHODS: Forty-one patients, aged 34-79 years, were studied during diagnostic cardiac catheterization. Aortic pressures were measured using a catheter-tip manometer at two points, one in the ascending aorta and one 40 cm distally in the descending aorta. Aortic AI was defined as the difference between early and late pressure peaks divided by the pulse pressure of the ascending aorta. Aortic PWV was calculated as the distance between the two measuring sites divided by the transit time. We also examined the effects of vasodilatation on AI and PWV by the intra-aortic administration of nitroglycerin in 15 patients. RESULTS: AI was significantly related to age, systolic aortic pressure, heart rate, left ventricular ejection time, and height. Aortic PWV showed an association only with age and systolic aortic pressure. There was no significant relationship between aortic AI and PWV (r = 0.28, NS). Nitroglycerin also produced different effects on aortic AI and PWV: aortic AI was significantly decreased (-0.17, P < 0.01) after nitroglycerin, but PWV remained unchanged (+0.4 m/s, NS). CONCLUSIONS: Aortic AI and PWV cannot be used interchangeably as an index of arterial stiffness. AI may not be a true indicator of arterial stiffness, but an index of wave reflection including PWV.

Adult↗

Serum BDNF, TNF-alpha and IL-1beta levels in dementia patients: comparison between Alzheimer's disease and vascular dementia.

Neurotrophins such as the brain-derived neurotrophic factor (BDNF) are reportedly related to the pathogenesis of Alzheimer's disease (AD). Several studies have revealed an alteration in BDNF expression in the postmortem brains of AD patients. BDNF has great potential as a therapeutic agent because of its ability to cross the blood-brain barrier and due to its wide in vivo distribution. However, little is known about in vivo BDNF in dementia patients. Moreover, the immunological function of neurotrophins such as BDNF has received great interest. Therefore, we investigated the serum levels of BDNF and cytokines such as TNF-alpha and IL-1beta in dementia patients by the enzyme-linked immunosorbent assay (ELISA). The following subjects were included in this study: 60 AD patients, 60 vascular dementia (VaD) patients and 33 healthy controls. AD and VaD patients were matched for age, gender and severity of dementia. Serum BDNF levels in AD patients were significantly lower than those in VaD patients and controls. TNF-alpha and IL-1beta levels showed no significant difference among the three groups. In the dementia groups, neither the TNF-alpha nor the IL-1beta levels correlated with the BDNF levels. Our results suggest that BDNF may play a pathological role in some cases of AD.

Aged↗

Edaravone diminishes free radicals from circulating neutrophils in patients with ischemic brain attack.

OBJECTIVE: Treatment with a free radical scavenger could be a new option for ischemic brain attack, however, little is known about the alteration of oxidative stress markers induced by edaravone, a novel free radical scavenger, in human ischemic brain attack. METHODS: We investigated the effects of edaravone on the oxidative stress markers in patients with ischemic brain attack. Twenty-one patients with ischemic brain attack and 19 controls were enrolled in this study. Blood samples were obtained just before and soon after the first administration of edaravone (30 mg) or ozagrel (40 mg). Intracellular reactive oxygen species of neutrophils were measured using 6-carboxy-2', 7'-dichlorodihydrofluorescin diacetate and a fluorescence-activated cell sorter. Superoxide from neutrophils, induced by phorbol myristate acetate (PMA), was determined by luminol-amplified chemiluminescence assay. RESULTS: Treatment with 30 mg of edaravone significantly decreased the intracellular reactive oxygen species (ROS) of neutrophils (Wilcoxon test, p=0.0001) and PMA-induced superoxide produced by neutrophils (Wilcoxon test, p=0.001). Ozagrel did not alter the intracellular ROS or superoxide production of neutrophils. CONCLUSION: Reduction of intracellular ROS and suppression of superoxide production in neutrophils provide a potential explanation for the clinical efficacy of edaravone in patients with ischemic brain attack.

Aged↗

A ribonucleoside with pyrimido[4,5-d]pyrimidine-2,4,5,7-(1H,3H,6H,8H)-tetraone as a nucleobase, which universally binds to natural nucleosides.

A ribonucleoside with pyrimido[4,5-d]pyrimidine-2,4,5,7-(1H,3H,6H,8H)-tetraone, which is expected to serve as a universal base, was synthesized and binding affinity of this artificial nucleoside to natural nucleosides was investigated by UV analysis. As the result, it was revealed that the artificial derivative universally forms a base pair with four kinds of natural deoxyribonucleosides.

Base Pairing↗

Narcolepsy without cataplexy: 2 subtypes based on CSF hypocretin-1/orexin-A findings.

STUDY OBJECTIVES: Cerebrospinal fluid (CSF) hypocretin-1 levels and their relationship with the clinical characteristics of narcolepsy without cataplexy have not been well elucidated. Our aim was to examine whether clinical characteristics vary with CSF hypocretin-1 levels among narcoleptic patients without cataplexy. DESIGN: Clinical features, variables on the multiple sleep latency test, and results of HLA typing were correlated with CSF hypocretin-1 levels. SETTING: University-based sleep laboratories and a sleep disorders center. PATIENTS: Seventeen patients (5 male, 12 female) who fulfilled the diagnostic criteria of narcolepsy without cataplexy according to the International Classification of Sleep Disorders. INERVENTIONS: Patients underwent lumbar puncture for CSF sampling. MEASUREMENTS AND RESULTS: Five patients showed a markedly decreased CSF hypocretin-1 level, whereas the remaining 12 patients showed almost normal levels. The mean rapid eye movement (REM) latency was significantly shorter and the age at onset was significantly earlier in the low CSF hypocretin-1 group compared with the normal CSF hypocretin-1 group. HLA-DR2 was positive in all of the patients with low CSF hypocretin-1, whereas only 33.3% of patients with normal CSF hypocretin-1 were DR2 positive. CONCLUSIONS: Some narcoleptic patients without cataplexy have low CSF hypocretin-1 levels. In patients who have narcolepsy without cataplexy, short mean REM latency, younger age at onset, and HLA-DR2 are associated with CSF hypocretin-1 deficiency. Markedly decreased CSF hypocretin-1 levels could be a significant marker for identifying subgroups of narcolepsy patients without cataplexy.

Adolescent↗

Prevention of cancer cachexia by a novel nuclear factor {kappa}B inhibitor in prostate cancer.

PURPOSE: To investigate the association between serum interleukin-6 (IL-6) and cachexia in patients with prostate cancer and the inhibitory effect of a new nuclear factor kappaB (NF-kappaB) inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on IL-6 production and cachexia in an animal model of hormone-refractory prostate cancer. EXPERIMENTAL DESIGN: The association between serum IL-6 levels and variables of cachexia was evaluated in 98 patients with prostate cancer. The inhibitory effects of DHMEQ on IL-6 secretion and cachexia were investigated in in vitro and in vivo studies using JCA-1 cells derived from human prostate cancer. RESULTS: Serum IL-6 levels were significantly elevated and cachexia developed in JCA-1 tumor-bearing mice as well as in prostate cancer patients with progressive disease. IL-6 secretion was significantly inhibited in JCA-1 cells exposed to DHMEQ. Intraperitoneal administration of DHMEQ (8 mg/kg) to tumor-bearing mice produced a significant amelioration of the reduction in body weight, epididymal fat weight, gastrocnemius muscle weight, hematocrit, and serum levels of triglyceride and albumin when compared with administration of DMSO or no treatment. DHMEQ caused a significant decrease of serum IL-6 level in JCA-1 tumor-bearing mice (all P < 0.05). CONCLUSIONS: These results suggested an association between serum IL-6 and cachexia in patients with prostate cancer and in JCA-1 tumor-bearing mice and that a new NF-kappaB inhibitor, DHMEQ, could prevent the development of cachexia in JCA-1 tumor-bearing mice presumably through the inhibition of IL-6 secretion. DHMEQ seems to show promise as a novel and unique anticachectic agent in hormone-refractory prostate cancer.

Albumins↗

MRI reveals fetus in fetu in the mediastinum.

Fetus in fetu is an extremely rare condition in which a fetiform calcified mass is contained within the newborn or infant, often in the retroperitoneal cavity. We report a case of a fetus in fetu in the posterior mediastinum of a newborn. The prospective diagnosis was made by fetal US and MRI and confirmed by postnatal plain radiograph, CT and MRI.

Diseases in Twins↗

Transient swelling of peripheral nerves in a case of neurosarcoidosis.

We present a case of neurosarcoidosis showing bilateral carpal tunnel syndrome which disappeared without any medication. This patient was also suffering from motor and sensory disturbance caused by peripheral neuropathy of the four extremities. Magnetic resonance image showed transient swelling of the median nerve, and subperineurial edema was unexpectedly observed in some fascicles in sural nerve biopsy. We hypothesize that the carpal tunnel syndrome in this case was induced by the intercanal high pressure due to edema inside the tunnel, which might be related to the high level of serum IL-2.

Aged↗

Solitary fibrous tumor of the prostate.

Solitary fibrous tumor of the prostate is extremely rare. Only five cases have been reported to the present. A 36-year-old man presented to our hospital complaining of difficulty in urination. Retrograde urethrography and urethroscopy demonstrated intraurethral protrusion of the left prostatic lobe and complete obstruction of prostatic urethra. Magnetic resonance imaging demonstrated the prostatic tumor with prominent intravesical protrusion. Transrectal echo-guided biopsy was performed on the supposition of leiomyosarcoma of prostate. However, the tumor was diagnosed as benign fibrous tumor, so the patient underwent transurethral resection of left prostatic lobe for the purpose of improving urinary condition, avoiding retrograde ejaculation. Histologic examination revealed a dense proliferation of spindle cells with no nuclear atypia. No mitotic figure was seen. The pathologic diagnosis was benign solitary fibrous tumor of the prostate, because the tumor was positive for CD34 and negative for alpha-smooth muscle actin and desmin by immunohistochemical study. The patient remained well without regrowth of the tumor during the last six years.

Adult↗

Suppression of hormone-refractory prostate cancer by a novel nuclear factor kappaB inhibitor in nude mice.

We have synthesized and explored the feasibility of using a novel nuclear factor (NF) kappaB inhibitor, a dehydroxymethylepoxyquinomicin designated as DHMEQ, against prostate cancer. The activity of NFkappaB, evaluated by transient transfection of a luciferase reporter DNA containing a specific binding sequence for NFkappaB, was inhibited by DHMEQ in three human hormone-refractory prostate cancer cell lines, DU145, JCA-1, and PC-3. Statistically significant growth inhibition was achieved by 20 micro g/ml of DHMEQ, and marked levels of apoptosis were induced 48 h after DHMEQ administration in vitro. Electrophoretic mobility shift assay showed that DHMEQ completely inhibited NFkappaB DNA binding activity in JCA-1 cells. Furthermore, i.p. administrations of DHMEQ significantly inhibited pre-established JCA-1 s.c. tumor growth in nude mice without any side effects. Our result indicates the possibility of using a novel NFkappaB activation inhibitor, DHMEQ, as a new treatment strategy against hormone-refractory prostate cancer.

Animals↗

Cervical and intracranial atherosclerosis and silent brain infarction in Japanese patients with coronary artery disease.

PURPOSE: To investigate the prevalence of cervical and intracranial atherosclerosis and silent brain infarction in patients with coronary artery disease (CAD). METHODS: Cervical and intracranial atherosclerotic lesions on magnetic resonance angiography (MRA) and silent brain infarctions on magnetic resonance imaging (MRI) were investigated in comparison with the findings of coronary angiography in 133 consecutive patients with CAD. RESULTS: The mean severity scores of cervical and intracranial MRA lesions were significantly higher in the three-vessel CAD (0.40 and 0.53, respectively) than in the zero-vessel CAD group (0.04 and 0.11). The mean scores of the maximal size and multiplicity of MRI lesion were also significantly greater in the two-vessel (1.00 and 1.44) and three-vessel CAD (0.94 and 1.26) than in the zero-vessel CAD group (0.27 and 0.50). The incidence of MRA lesion was markedly higher in patients with brain MRI lesion than in those without (51.1 vs. 6.5%). CONCLUSIONS: Serious coronary artery lesions were commonly accompanied by latent atherosclerotic lesions in the cervical and intracranial arteries besides silent brain infarction in patients with CAD.

Adult↗

Antitumor effect of a novel nuclear factor-kappa B activation inhibitor in bladder cancer cells.

Nuclear factor (NF)-kappaB is a transcription factor that not only induces and controls various genes, including those of inflammatory cytokines, but also activates genes which suppress apoptosis. It has been clearly demonstrated that certain advanced human bladder cancer cells constitutively acquire the ability to activate NF-kappaB, which not only protects cancer cells from apoptotic cell death, but also upregulates the production of various cytokines that may increase the malignant potential of the disease and cause paraneoplastic syndromes. The NF-kappaB inhibitors may therefore be useful as anticancer agents. An NF-kappaB function inhibitor, a dehydroxymethyl derivative of epoxyquinomicin C (DHMEQ), has recently been designed and synthesized. The effectiveness of DHMEQ against advanced human bladder cancer cell line KU-19-19, in which NF-kappaB is constitutively activated, has been investigated. The DNA-binding activity of NF-kappaB was completely inhibited following 2-6-h exposure to 10 microg/ml of DHMEQ. Marked levels of apoptosis were observed 48 h after DHMEQ administration. These results confirmed that NF-kappaB activation maintains the viability of KU-19-19 cells, that DHMEQ inhibited constitutively activated NF-kappaB, and, consequently, apoptosis was induced. However, it was still possible that DHMEQ caused apoptotic cell death through some other mechanism which has not yet been fully investigated. The authors conclude that DHMEQ could represent a new treatment strategy against advanced bladder cancer.

Animals↗

[A survey of deaths of homeless people in Osaka City].

OBJECTIVE: Problems of homelessness have been worsening recently in urban areas in Japan. The purpose of this study was to clarify the number and nature of deaths of homeless people in Osaka City. METHODS: All deaths of homeless people in 2000 in Osaka City were examined by reviewing the records of abnormal deaths kept at the Osaka Prefecture Medical Examiner's Office and the records of autopsies at the Department of Legal Medicine, Osaka University. Homeless people in this study were defined as those who were living on the street or staying in flophouses. RESULTS: A total of 294 deaths of homeless were identified, 213 of those who lived on the street and 81 of those who stayed in flophouses. The average age at death was 56.2 years old. Of those who had money on them when they were found, half had only 1,000 yen or less. Of the total death, 172 (59%) died of disease, 47 (16%) of suicide, 6 (2%) of homicide, and 43 (15%) of accidents including 8 from starvation and 12 from cold. Causes of death from disease were identified with the following order of frequencies: cardiac disease, hepatitis and cirrhosis, pneumonia, lung tuberculosis, cerebrovascular disease, malnutrition, malignant neoplasm and peptic ulcer. All those who died of malnutrition, starvation and cold were more than 40 years old and had less money on them at their death than the others. Malnutrition and starvation occurred throughout the year, while deaths from cold were concentrated in winter, especially in February. Standardized mortality ratios (SMRs) for homeless men living on the street in Osaka City were calculated with Japanese males as the standard population. The SMR for all causes of death was 3.6, for cardiac disease 3.3, for pneumonia 4.5, for tuberculosis 44.8, for hepatitis and cirrhosis 4.1, for peptic ulcer 8.6, for suicide 6.0, and for homicide 78.9. All these figures were statistically significantly higher than for the standard population. CONCLUSION: Our results show that most homeless people die untimely from preventable causes such as pneumonia, malnutrition and starvation. This suggests that these people are not provided with the necessary health care.

Adult↗