Biomedical subjects

H Hayakawa

Publications and source records attributed to H Hayakawa.

At least 19 recordsLinked to original sources

PubMed2004

Solar wind-induced atmospheric erosion at Mars: first results from ASPERA-3 on Mars Express.

The Analyzer of Space Plasma and Energetic Atoms (ASPERA) on board the Mars Express spacecraft found that solar wind plasma and accelerated ionospheric ions may be observed all the way down to the Mars Express pericenter of 270 kilometers above the dayside planetary surface. This is very deep in the ionosphere, implying direct exposure of the martian topside atmosphere to solar wind plasma forcing. The low-altitude penetration of solar wind plasma and the energization of ionospheric plasma may be due to solar wind irregularities or perturbations, to magnetic anomalies at Mars, or both.

Journal Article↗

PubMed2004

High frequency Agrobacterium-mediated transformation and plant regeneration via direct shoot formation from leaf explants in Beta vulgaris and Beta maritima.

We have developed a new procedure for Agrobacterium-mediated transformation of plants in the genus Beta using shoot-base as the material for Agrobacterium infection. The frequency of regeneration from shoot bases was analyzed in seven accessions of sugarbeet ( Beta vulgaris) and two accessions of B. maritima to select materials suitable for obtaining transformed plants. The frequency of transformation of the chosen accessions using Agrobacterium strain LBA4404 and selection on 150-mg/l kanamycin was found to be higher than that in previously published methods. Genomic DNA analysis and beta-glucuronidase reporter assays showed that the transgene was inherited and expressed in subsequent generations. In our method, shoot bases are prepared by a simple procedure, and transformation does not involve the callus phase, thus minimizing the occurrence of somaclonal variations.

Agrobacterium tumefaciens↗

PubMed2003

Lack of evidence for a role of Epstein-Barr virus in the increase of lung cancer in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is known as an independent risk factor for lung cancer. Because Epstein-Barr virus (EBV) may be involved in the genesis of IPF as well as certain malignancies, we investigated whether EBV contributes to the increased incidence of lung cancer in IPF The formalin-fixed and paraffin-embedded lung sections were prepared from 22 lung cancer patients with IPF and 22 lung cancer patients without IPF All ofthe IPF patients pathologically showed usual interstitial pneumonia. In situ hybridization for EBV-encoded small non-polyadenylated RNAs failed to show positive signals in the cancer tissues of either IPF or non-IPF patients. This study did not provide evidence for an etiologic role of EBV in the development of lung cancer in IPF.

Adenocarcinoma↗

PubMed2002

Feasibility of ex vivo gene therapy for neurological disorders using the new retroviral vector GCDNsap packaged in the vesicular stomatitis virus G protein.

Neuronal progenitor cells (NPC) are particularly suited as the target population for genetic and cellular therapy of neurological disorders such as Parkinson's disease or stroke. However, genetic modification of these cells using retroviral vectors remains a great challenge because of the low transduction rate and the need for fetal calf serum (FCS) during the transduction process that induces the cell differentiation to mature neurons. To overcome these problems, we developed a new retrovirus production system in which the simplified retroviral vector GCDNsap engineered to be resistant to denovo methylation was packaged in the vesicular stomatitis virus G protein (VSV-G), concentrated by centrifugation, and resuspended in serum-free medium (StemPro-34 SFM). In transduction experiments using enhanced green fluorescent protein (EGFP) as a marker, the concentrated FCS-free virus supernatant infected NPC at a high rate, while maintaining the ability of these cells to self-renew and differentiate in vitro. When such cells were grafted into mouse brains, EGFP-expressing NPC were detected in the region around the injection site at 8 weeks post transplantation. These findings suggest that the gene transfer system described here may provide a useful tool to genetically modify NPC for treatments of neurological disorders.

Animals↗

PubMed2001

An AAV-derived Apaf-1 dominant negative inhibitor prevents MPTP toxicity as antiapoptotic gene therapy for Parkinson's disease.

Adeno-associated virus (AAV) vector delivery of an Apaf-1-dominant negative inhibitor was tested for its antiapoptotic effect on degenerating nigrostriatal neurons in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. The wild-type caspase recruitment domain of Apaf-1 was used as a dominant negative inhibitor of Apaf-1 (rAAV-Apaf-1-DN-EGFP). An AAV virus vector was used to deliver it into the striatum of C57 black mice, and the animals were treated with MPTP. The number of tyrosine hydroxylase-positive neurons in the substantia nigra was not changed on the rAAV-Apaf-1-DN-EGFP injected side compared with the noninjected side. We also examined the effect of a caspase 1 C285G mutant as a dominant negative inhibitor of caspase 1 (rAAV-caspase-1-DN-EGFP) in the same model. However, there was no difference in the number of tyrosine hydroxylase-positive neurons between the rAAV-caspase-1-DN-EGFP injected side and the noninjected side. These results indicate that delivery of Apaf-1-DN by using an AAV vector system can prevent nigrostriatal degeneration in MPTP mice, suggesting that it could be a promising therapeutic strategy for patients with Parkinson's disease. The major mechanism of dopaminergic neuronal death triggered by MPTP seems to be the mitochondrial apoptotic pathway.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2001

Specific binding of 8-oxoguanine-containing RNA to polynucleotide phosphorylase protein.

8-Oxoguanine, an oxidized form of guanine, has the potential to pair with both cytosine and adenine, and thus, the persistence of this base in messenger RNA would cause translational errors. To prevent such an outcome, organisms probably have a mechanism for recognizing RNA molecules carrying 8-oxoguanine and prevent them from entering into the cellular translational machinery. We now report that the Escherichia coli cell possesses proteins that bind specifically to RNA carrying 8-oxoguanine. On incubation with a cell-free extract, 8-oxoguanine-containing RNA is stable while normal RNA is degraded by cellular nucleases. The RNase protection assay and gel shift assay revealed that some proteins bind specifically to 8-oxoguanine-containing RNA, hence preventing nuclease attacks. Among the complexes that were detected, one with a 77 kDa protein exhibits tight binding between RNA and protein components. This protein was identified as polynucleotide phosphorylase, encoded by the pnp gene. pnp(-)() mutants are hyperresistant to paraquat, a drug that induces oxidative stress in the cell. Binding of Pnp protein to 8-oxoguanine-containing RNA would inhibit cell growth, probably due to withdrawal of such RNA from the translational machinery. The Pnp protein may, therefore, discriminate between an oxidized RNA molecule and a normal one, thus contributing a high fidelity of translation.

Binding, Competitive↗

PubMed2001

Three-year follow-up of patients with right bundle branch block and ST segment elevation in the right precordial leads: Japanese Registry of Brugada Syndrome. Idiopathic Ventricular Fibrillation Investigators.

OBJECTIVES: We sought to determine the prevalence of right bundle branch block (RBBB) and ST segment elevation in the working Japanese population, as well as the event rate during a three-year prospective follow-up period. BACKGROUND: A poor prognosis of RBBB and ST segment elevation has been reported in Europe and South America, even in asymptomatic patients; however, a large population of asymptomatic patients with sporadic RBBB and ST segment elevation has not been studied. METHODS: Ten thousand 12-lead electrocardiograms (ECGs) were obtained during annual check-ups of working adults in the Tokyo area. This three-year prospective follow-up study consisted of 105 patients, including 20 with ventricular fibrillation, 18 with syncope and 67 who were asymptomatic. They were registered from 46 institutions in Japan. RESULTS: The prevalence of ECG abnormalities in working adults was 0.16%. A coved-type ST segment elevation was related to a history of cardiac events, and 18% of registered patients had PR prolongation and 9.5% had left-axis deviation. The cumulative cardiac event-free rate was 67.6% in the symptomatic group and 93.4% in the asymptomatic group (p = 0.0004) after three years. CONCLUSIONS: The recurrence rate of cardiac events in symptomatic patients was similar to that reported previously, but it was very low in sporadic asymptomatic patients. The ECG findings may help us to select patients for further examination and more accurate evaluation of their prognoses.

Adult↗

PubMed2001

Observation of spin-orbit splitting in lambda single-particle states.

The spin-orbit splitting of Lambda single-particle states in (13)(Lambda)C was measured. The 13C(K-,pi(-))(13)(Lambda)C reaction was used to excite both the 1/2(-) and 3/2(-) states simultaneously, which have predominantly 12C(0(+)) x p(Lambda) configuration. gamma rays from the states to the ground state were measured in coincidence with the pi(-)'s, by which ls splitting was found to be 152+/-54(stat)+/-36(syst) keV. The value is 20-30 times smaller than exhibited by the ls splitting in the nuclear shell model. This value gives us new insight into the YN interaction.

Journal Article↗

PubMed2001

Plasma levels of natriuretic peptides in relation to doxorubicin-induced cardiotoxicity and cardiac function in children with cancer.

BACKGROUND: Anthracyclines are effective anticancer drugs for childhood cancer with dose-limiting cardiotoxicity. Children who have received anthracyclines thus need periodical cardiac evaluation. The plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) have been shown to increase in proportion to severity of cardiac dysfunction. We examined whether plasma levels of ANP and BNP, in addition to echocardiographic evaluation, can be used as specific markers for doxorubicin-induced cardiotoxic effects in children. PROCEDURE: Consecutively, 34 patients (18 boys and 16 girls) who had previously received doxorubicin-containing chemotherapy were enrolled in this study. Plasma ANP and BNP were assayed simultaneously at the time of first cardiac function evaluation by echocardiography. RESULTS: Of the 34 patients, 8 (23.5%) had left ventricular dysfunction as assessed by echocardiography. Both ANP and BNP plasma levels in these patients were significantly elevated in comparison with healthy controls (P < 0.01) or patients with normal cardiac function (P < 0.05). It should be also noted that ANP and BNP levels were correlated significantly with cardiac systolic function, but not with diastolic function. CONCLUSIONS: These results suggest that plasma ANP and BNP levels could be markers for doxorubicin-induced cardiotoxicity in children. Measurement of natriuretic peptide levels during treatment may allow earlier-identification of individuals at risk for severe cardiac damage.

Adolescent↗

PubMed2001

Effects of intracavernous administration of adrenomedullin on erectile function in rats.

We have reported that adrenomedullin (AM)-induced vasodilation is at least in part nitric oxide (NO)-cGMP-dependent in the rat. Although it is well known that NO is much involved in the erectile function, it is controversial as to whether AM influences the erectile function. Thus, we examined the effects of AM on intracavernous pressure (ICP) during penile erection. The left carotid artery of rats was cannulated to monitor of mean arterial pressure (MAP). Bipolar electrodes were positioned on the cavernous nerve. The right cavernous body was cannulated with a needle connected to a pressure transducer to monitor ICP. Electrical stimulation (ES) increased ICP in a voltage-dependent manner. Elevation of ICP continued during ES. The intracavernous injection of 0.5 nmol AM significantly potentiated ES-induced increases in both maximal developed ICP/MAP and area under the curve (ICP trace; AUC). Since AM slightly lowered MAP, ICP was normalized by MAP. i.v. administration of N(omega)-nitro-L-arginine, a NO synthase inhibitor, markedly decreased AM/ES-induced ICP elevation. However, in the presence of E-4021, a cGMP-specific phosphodiesterase inhibitor, AM further increased both ICP/MAP and AUC. These results suggest that a NO-cGMP pathway is involved in the regulation of AM-induced rat cavernous vasorelaxation.

Adrenomedullin↗

PubMed2001

Clinical significance of potential pathogenic microorganisms of sputum in patients with pulmonary tuberculosis.

BACKGROUND: Bacterial culture of sputum is frequently positive in patients with pulmonary tuberculosis (TB). However, it remains to be clarified whether detection of potential pathogenic microorganisms (PPM) in sputum represents bacterial infection or only colonization of the respiratory tract. In the present study, we investigated the clinical significance of PPM in patients with pulmonary TB. METHODOLOGY: Sputum culture for PPM was studied in 174 pulmonary TB patients (117 males and 57 females, mean age of 71 years) on the day of admission. Ninety-seven patients (63 males and 34 females, mean age of 67.1 years) also underwent transtracheal aspirates (TTA). Quantitative culture of sputum and TTA was performed to distinguish infection from colonization. The results were evaluated as follows: more than 106 or 105 c.f.u./mL indicated infection in the case of sputum or TTA samples, respectively. We also compared various clinical parameters between patients with PPM and patients with non-potential pathogenic microorganisms (non-PPM). RESULTS: Potential pathogenic microorganisms were positive in 44% and 24% of sputum and TTA specimens, respectively. However, quantitative culture for PPM showed positive findings in only 11% and 3% of sputum and TTA specimens, respectively. A comparative study of the clinical features revealed that PPM patients had a lower bodyweight and lower serum albumin levels than non-PPM patients. A fatal outcome was also more common in PPM patients than in non-PPM patients. Logistic regression analysis further confirmed that PPM clearly contributed to a fatal outcome in addition to the previously established parameters including age, performance status, haemoglobin, albumin and radiographic disease extent. CONCLUSION: Although sputum PPM represent only colonization of the upper respiratory tract in TB patients, they are associated with a poor prognosis.

Aged↗

PubMed2001

Prognosis of acute poststreptococcal glomerulonephritis (APSGN) is excellent in children, when adequately diagnosed.

BACKGROUND: Recently, the prognosis of acute poststreptococcal glomerulonephritis (APSGN) has been reported as improved, compared with the results of previous studies. In an attempt to clarify this, we analyzed the clinical course of patients with APSGN. METHODS: A total of 220 children with acute nephritic syndrome were treated in the affiliated hospitals of our department, between January 1988 and December 1997. Among them, 138 children who were diagnosed with APSGN according to the presence of hematuria, transient hypocomplementemia and evidence of group A beta-hemolytic streptococcal infection, were studied. RESULTS: Serum creatinine and blood urea nitrogen levels at onset were 0.5 +/- 0.2 mg/dL and 20 +/-12 mg/dL, respectively. There were no patients with renal dysfunction (serum creatinine level > or = 1.5 mg/dL), but one patient with nephrotic syndrome. Blood pressure was well controlled in all patients and there were no patients with persistent hypertension. Serum complement levels were normalized within 12 weeks (100%), hematuria disappeared within 4 years (100%) and proteinuria disappeared within 3 years (100%) from the onset. CONCLUSIONS: These data indicate that the prognosis of APSGN during childhood is excellent, when adequately diagnosed and treated.

Acute Disease↗

PubMed2001

Intracerebral haematoma: traumatic or non-traumatic.

A 35-year-old woman, a chronic alcoholic, died from an intracerebral haematoma 10 hr after she fell downstairs. Some subcutaneous bleeding was seen on the head and face, but there were no new skull fractures and surface contusions of the brain. She appeared to have few predisposing conditions for non-traumatic cerebral haemorrhage. In addition, the haematoma was mainly located "lateral" to the basal ganglia, not where hypertensive bleeding most commonly occurs, and subdural and haemorrhage in the corpus callosum was found with subdural/and subarachnoid haemorrhage. We concluded that on falling a shearing strain from a rotating force produced the intracerebral haemorrhage, but without skull fractures and surface contusions of the brain. She had been admitted to a neurosurgical hospital just 11 months before this incident because of an epidural haemorrhage with left temporal bone fracture. Mild thrombocytopenia was found during that hospitalization. In this report, this abnormality was thought to have some relation to the formation of the huge haematoma occurring after the intracerebral bleeding started.

Journal Article↗

PubMed2001

Synthesis and antiviral evaluation of alpha-D-2',3'-didehydro-2',3'-dideoxy-3'-C-hydroxymethyl nucleosides.

A series of hydroxymethyl branched analogues of antiviral apio d4Ns was synthesized from D-arabinose. The SN2' ring opening reaction of 2,2'-anhydro-alpha-D-pyrimidinenucleoside (10) was mainly investigated. The reaction selectively gave SN2' adducts, which were deprotected to furnish the desired alpha-D-2',3'-didehydro-2',3'-dideoxy-3'-C-hydroxymethyl nucleosides (2).

Antiviral Agents↗

PubMed2001

Multicenter prospective nonrandomized study of long-term antiarrhythmic drug therapy in patients with tachyarrhythmias: Japanese Antiarrhythmics Long-Term Study-2 (JALT-2 Study).

Based on the results of the Cardiac Arrhythmia Suppression Trial (CAST), strategies for the treatment of tachyarrhythmias have changed rapidly. The Japanese Antiarrhythmics Long-Term (JALT) study was planned to investigate the present methods for choosing antiarrhythmic drugs, and the effects on long-term prognosis in patients with tachyarrhythmias in Japan. Following a 6-month preliminary study (JALT-1), there was a multicenter nonrandomized prospective study (JALT-2), with a 2-year follow-up, of patients with paroxysmal atrial fibrillation (PAF), sustained ventricular tachycardia (SVT) and nonsustained VT (NSVT). Four hundred fifty-five patients were registered, and 361 of them (79%) were analyzed. Cerebral infarction occurred in 10 of 193 patients (5.2%) with PAF. Transition to chronic AF was observed in 21 patients (10.9%), but in none of the patients receiving Ca antagonist therapy. Twenty-five patients died: 5 deaths were arrhythmic, 10 were because of pump failure, and 9 were noncardiac. The most significant difference in drug selection between JALT-1 and JALT-2 was the increase in the use of slow kinetic Na channel blockers for PAF and the decrease in the use of the same agents for VT in the JALT-2 study. A marked change of therapeutic strategy occurred in JALT-2 compared with JALT-1. Most patients with a poor prognosis had underlying heart diseases and heart failure, but the per annum rate of death by arrhythmia and pump failure in JALT-2 was less than that in JALT-1.

Adult↗

PubMed2001

Non-invasive diagnosis of concealed Wolff-Parkinson-White syndrome by detection of concealed anterograde pre-excitation.

Electrophysiological findings suggest that concealed anterograde conduction through accessory pathways may exist even during sinus rhythm in patients with so-called concealed Wolff-Parkinson-White (WPW) syndrome. To evaluate the pre-excitation characteristics in various types of WPW syndrome, high-resolution electrocardiograms were analyzed in 81 consecutive WPW syndrome patients and 50 age-matched normal subjects. The WPW group consisted of 30 cases of concealed WPW diagnosed by electrophysiological study, 38 cases of manifest WPW in which apparent delta waves were constant, and 13 cases of intermittent WPW in which the delta waves appeared periodically. The duration of the low-amplitude, high-frequency components of the signal-averaged filtered QRS complex that preceded the earliest upstroke of the surface QRS, including any delta waves (preceding potential duration, PPD), and the duration of low amplitude signals less than 10 microV (I-LAS10) or 20 microV (I-LAS20) were measured as parameters of pre-excitation. The PPDs in concealed and intermittent WPW were both significantly longer than in manifest WPW or in control subjects (6.8+/-2.7 ms, 7.9+/-3.5 ms vs 2.3+/-3.2 ms, 1.0+/-1.6 ms, both p<0.0001). Abnormally prolonged PPDs (>4 ms) were observed in 90% of concealed WPW cases and 76.9% of intermittent WPW, but in only 4% of normal subjects and 31.6% of manifest WPW. Both I-LAS10 and I-LAS20 in the 3 types of WPW syndrome were significantly longer than in normal subjects. The initial portion of the filtered QRS in concealed WPW closely resembled that of intermittent WPW. These results strongly suggest that in concealed WPW anterograde conduction through accessory pathways does occur and produces small amounts of pre-excitation even during sinus rhythm. The study concluded that, despite its name, concealed WPW is not completely concealed, and that non-invasive diagnosis during sinus rhythm is possible by using high-resolution electrocardiography to detect the concealed anterograde pre-excitation.

Electrocardiography↗

PubMed2001

[Detection of beat-to-beat changes in high frequency components of the QRS complex using a free optimal signal averaging system: relationship with ventricular arrhythmias].

In this study, we evaluated the relationship between beat-to-beat changes in high frequency components of the QRS complex and ventricular arrhythmias by using a newly developed event-related (ER) signal averaging technique. The study involved 82 patients with premature ventricular contractions (PVC), 56 of whom, including 16 with ventricular tachycardia (VT), were enrolled in Analysis I. In Analysis I, averaged sinus beats were classified into three patterns: 1) the sinus beat immediately before PVC (BEF); 2) that immediately after PVC (AFT); and 3) all sinus beats (ALL). Analysis II covered the remaining 26 patients, and involved five modes of event-related signal averaging, using: 1) the second beat preceding PVC (2-B); 2) the beat immediately preceding PVC (1-B); 3) the beat immediately after PVC (1-A); 4) the second beat after PVC (2-A); and 5) the beat isolated (ISO) from PVC. The filtered QRS duration (F-QRS) and the integral voltage of the terminal 40 msec (RMS 40-I) were measured using these averaging patterns. F-QRS in the VT group was longer than that in the non-VT group, but RMS 40-I was shorter. The F-QRS of BEF (1-B) was significantly longer than that of AFT (1-A). The transient difference in the F-QRS was observed in both VT and non-VT groups. This difference was almost eliminated at AFT (1-A) in the non-VT group, but was stable at AFT (1-A) in the VT group. Simultaneousely, RMS 40-I in BEF was significantly shorter than that in AFT. This transient decrease of RMS 40-I was observed in both VT and non-VT groups. Although RMS 40-I after this decrease showed a return almost to the control level at AFT in the non-VT group, it tended to remain even at AFT in the VT group. The sudden prolongation of F-QRS that occurred with the RMS 40-I decrease in BEF was related to the appearance of PVCs. We attributed the fact that these changes in F-QRS and RMS 40-I were observed even at AFT in the VT group to electrophysiologically preferable conditions for reentry.

Electrocardiography↗

PubMed2001

Tissue inhibitor of metalloproteinases 1 and 2 directly stimulate the bone-resorbing activity of isolated mature osteoclasts.

Tissue inhibitor metalloproteinases 1 (TIMP-1) and 2 have been reported to inhibit bone resorption. However, here, we report the direct action of both TIMP-1 and TIMP-2 on isolated rabbit mature osteoclasts to stimulate their bone-resorbing activity at significantly lower concentrations (approximately ng/ml) than those (approximately microg/ml) required for the inhibition of bone resorption. The cell population used in this study consisted of a mature osteoclast population with >95% purity. TIMP-1 (approximately 50 ng/ml) and TIMP-2 (approximately 8-10 ng/ml) increased the pit area excavated by the isolated mature osteoclasts. The stimulatory effects of TIMPs were abolished by simultaneous addition of anti-TIMP antibodies. At higher concentrations, the stimulation of bone resorption decreased reversely to the control level. The magnitude of the stimulatory effect of TIMP-2 was more than that of TIMP-1. Metalloproteinase inhibitors such as BE16627B and R94138 could not replace TIMPs with respect to the bone-resorbing activity, suggesting that the osteoclast-stimulating activity of TIMPs was independent of the inhibitory activity on matrix metalloproteinases (MMPs). TIMPs stimulated tyrosine phosphorylation of cellular proteins in the isolated mature osteoclasts. Both herbimycin A, an inhibitor of tyrosine kinases, and PD98059 and U0126, inhibitors of mitogen-activated protein kinase (MAPK), completely blocked the TIMP-induced stimulation of osteoclastic bone-resorbing activity. On the plasma membrane of osteoclasts, some TIMP-2-binding proteins were detected by a cross-linking experiment. These findings show that TIMPs directly stimulate the bone-resorbing activity of isolated mature osteoclasts at their physiological concentrations and that the stimulatory action of TIMPs is likely to be independent of their activities as inhibitors of MMPs.

Acetamides↗