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Biomedical subjects

H Yoneda

Publications and source records attributed to H Yoneda.

At least 19 recordsLinked to original sources

The role of cyberknife radiosurgery/radiotherapy for brain metastases of multiple or large-size tumors.

OBJECTIVE: Focused, highly targeted radiosurgery and fractionated radiotherapy using the Cyberknife are useful treatments for multiple or large metastases. Here we present our results of Cyberknife radiosurgery for 71 patients with 148 metastatic brain lesions. METHODS: There were 32 women and 39 men with a median age of 63 (range: 30-88) years. Radiographic follow-up was available for 60 patients with 104 lesions. The mean and median initial volumes of the tumor per lesion were 6.6 and 2.9 cm(3) (range: 0.1-53.2 cm(3)), respectively, at the time of the initial Cyberknife treatment. Forty patients (56%) had a single lesion, and 31 (44%) had multiple lesions (range: 2-7) at initial treatment. The number of fractions ranged from 1 to 3, and forty (27%) of 148 lesions were treated by a fractionated course of Cyberknife therapy. The mean marginal dose was 20.2 Gy (range 7.8-30.1 Gy, median: 20.7 Gy). RESULTS: At 44 weeks of median follow-up, there were no permanent symptoms resulting from radiation necrosis. Overall 6-month and 1-year survival rates were 74% and 47%, respectively, and the median survival time was 56 weeks. The Karnofsky performance score and extracranial metastasis were significant prognostic factors at 6 months and 1 year, respectively, in both univariate and multivariate analyses. Age or multiple metastases did not influence prognosis at 6 months and 1 year. Local control was achieved in 83% (86 lesions). After additional radiosurgical or surgical salvage, no patient died as a result of intracranial disease. Twenty-five patients developed 92 new metastases (range 1-13) outside of the treated lesions with 22.4 weeks of median follow-up. Among them, 21 patients (84 lesions) were treated by salvage Cyberknife. CONCLUSION: Despite the inclusion of an unfavorable group of patients with large tumors, our results for survival and tumor control rates are comparable to those of published series. The Cyberknife provides the advantage of allowing for fractionated treatment to multiple or large-size tumors.

Adult↗

No association with the calcineurin A gamma subunit gene (PPP3CC) haplotype to Japanese schizophrenia.

Calcineurin, one of the serine/threonine protein phosphatase, comprises more than 1% of the total protein content in brain. This evidence points towards important roles of calcineurin in neural function. Miyakawa et al. reported that forebrain-specific calcineurin knockout mice showed the behavioral abnormalities that are often observed in schizophrenia patients. Based on this evidence, they suggested that calcineurin dysfunction could be involved in schizophrenia pathogenesis. Thereafter this report, Gerber et al. performed transmission disequilibrium test (TDT) studies and showed an evidence for a nominally significant over-transmission of a common haplotype of the human calcineurin A gamma subunit gene (PPP3CC). We performed association analysis of PPP3CC in Japanese sample of 457 schizophrenia cases and 429 controls. To our regret, we could not confirm the association with Japanese schizophrenia to PPP3CC including core at-risk haplotype. Our result suggests that PPP3CC may not play a major role in Japanese schizophrenia.

Calcineurin↗

Fluctuation of extracellular hypocretin-1 (orexin A) levels in the rat in relation to the light-dark cycle and sleep-wake activities.

Hypocretins/orexins are neuropeptides implicated in sleep regulation and the sleep disorder narcolepsy. In order to examine how hypocretin activity fluctuates across 24 h with respect to the sleep-wake cycle, we measured changes in extracellular hypocretin-1 levels in the lateral hypothalamus and medial thalamus of freely moving rats with simultaneous sleep recordings. Hypocretin levels exhibited a robust diurnal fluctuation; levels slowly increased during the dark period (active phase), and decreased during the light period (rest phase). Levels were not correlated with the amount of wake or sleep in each period. Although an acute 4-h light-shift did not alter hypocretin levels, 6-h sleep deprivation significantly increased hypocretin release during the forced-wake period. Hypocretin activity is, thus, likely to build up during wakefulness and decline with the occurrence of sleep. These findings, together with the fact that a difficulty in maintaining wakefulness during the daytime is one of the primary symptoms of hypocretin-deficient narcolepsy, suggest that hypocretin activity may be critical in opposing sleep propensity during periods of prolonged wakefulness.

Animals↗

Cause-specific mortality risk among male alcoholics residing in the Osaka metropolitan area.

We evaluated the mortality risk among 306 male alcoholics living in Osaka, Japan, at the time of initial diagnosis between 1972 and 1983, with regard to the cause of death, length of time from diagnosis, and participation in an alcohol abstinence self-help group. By the closing date on 1 March 1992, 110 of the 306 alcoholics had died, yielding an observed-to-expected (O/E) ratio of 4.5 [95% confidence interval (CI) = 3.7-5.4]. The alcoholics had significantly elevated mortality risks from all malignant neoplasms (O/E = 2.1, 95%CI = 1.2-3.3), esophageal cancer (O/E = 8.4, 95%CI = 1.7-24.5), diseases of the circulatory system (O/E = 4.4, 95%CI = 3.0-6.2), liver cirrhosis (O/E = 15.9, 95%CI = 10.2-23.6), diseases of the genitourinary system (O/E = 6.3, 95%CI = 1.3-18.5), and external death (O/E = 10.3, 95%CI = 6.3-15.8). The mortality risk from all causes still remained significantly high beyond the tenth year following initial diagnosis (O/E = 2.6, 95%CI = 1.0-6.2). The mortality risks from liver cirrhosis and external death (such as suicide) were highest within the first year following diagnosis, and were still high beyond the tenth year. A significantly high mortality risk from diseases of the circulatory system was observed between the first and ninth years, and the mortality risk from all malignant neoplasms was significantly elevated beyond 10 years following diagnosis. Alcoholics who did not join a self-help group soon after the initial institutional treatment had different cause-specific and time-specific mortality risks from those who did join a self-help group. These findings show the importance of long-term clinical follow-up of male alcoholics, taking into consideration the cause-specific mortality.

Adult↗

Long-term outcome in 306 males with alcoholism.

The subjects of this study were 306 male alcoholics who lived in Osaka, Japan, and who were initially diagnosed with alcoholism at a psychiatric institution between 1972 and 1983. Follow-up studies were done on three occasions: 1 March 1985 (Time 1), 1 November 1988 (Time 2) and 1 March 1992 (Time 3). We followed up 232 (75.8%) of the 306 male alcoholics. By the end of the study period 110 (35.9%) of the subjects were deceased. Regarding cross-sectional sobriety status, from Time 1 to Time 3 the complete abstinence rate changed from 16.0 to 18.6%, excessive drinking rate was from 13.1 to 9.8%, and controlled drinking rate was from 6.9 to 9.8%. The longitudinal sobriety status of 122 living patients during the 5 years before the close of this study were: rate of stable abstinence, 28.7%; unstable abstinence, 21.3%; controlled drinking, 12.3%; and relapse 37.7%. Such variables as being without public assistance at the time of the initial diagnosis of alcoholism and attending a self-help group soon after the initial treatment were associated with stable abstinence. Age (20-39 years) and receiving outpatient treatment at the time of the initial treatment also emerged as predictors of survival. However, those variables, except attending a self-help group soon after the initial treatment, might merely indicate severity of alcoholism. For improving treatment results, it may be most important to provide a treatment environment within the residential area so that alcoholics may receive treatment at an early stage of alcoholism and attend a self-help group.

Adult↗

Prostaglandin E (EP) receptor subtypes and sleep: promotion by EP4 and inhibition by EP1/EP2.

Prostaglandin (PG) E2 reportedly augmented wakefulness when continuously infused into the third ventricle of the rat brain, whereas it promoted sleep when continuously infused into the subarachnoid space of the ventral surface zone of the rostral basal forebrain, which was designated previously as a PGD2-sensitive sleep-promoting zone (PGD2-SZ). In the present study, we investigated the effects of PGE (EP)-receptor agonists on sleep-wakefulness activities by infusing agonists into the third ventricle or into the subarachnoid space of the PGD2-SZ. Our results indicated that the waking effect is mediated by EP1 and EP2 receptors situating around the third ventricle, whereas the sleep-promoting effect is brought about mainly through activation of EP4 receptors located at or near the subarachnoid space of the PGD2-SZ.

Animals↗

Deficiency in mitochondrial aldehyde dehydrogenase increases the risk for late-onset Alzheimer's disease in the Japanese population.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) deficiency is caused by a mutant allele in the Mongoloids. To examine whether genetic constitutions affecting aldehyde metabolism influence the risk for late-onset Alzheimer's disease (LOAD), we performed a case-control study in the Japanese population on the deficiency in ALDH2 caused by the dominant-negative mutant allele of the ALDH2 gene (ALDH2*2). In a comparison of 447 patients with sex, age, and region matched nondemented controls, the genotype frequency carrying the ALDH2*2 allele was significantly higher in the patients than in the controls (48.1% vs 37.4%, P = 0.001). Logistic regression analysis indicates that carriage of the ALDH2*2 allele is an independent risk for LOAD of the epsilon4 allele of the apolipoprotein E gene (APOE-epsilon4) (P = 0.002). Moreover, the odds ratio for LOAD in carriers of the ALDH2*2 allele was almost twice that in noncarriers, irrespective of status with regard to the APOE-epsilon4 allele. Among patients homozygous for the APOE-epsilon4 allele, age at onset of LOAD was significantly lower in those with than without the ALDH2*2 allele. In addition, dosage of the ALDH2*2 allele significantly affected age at onset of patients homozygous for the APOE-epsilon4 allele. These results indicate that the ALDH2 deficiency is a risk for LOAD, synergistically acting with the APOE-epsilon4 allele.

Age of Onset↗

Effects of imidapril and captopril on streptozotocin-induced diabetic nephropathy in mice.

We investigated whether the prevention of the development of diabetic nephropathy by angiotensin-converting enzyme inhibitors is associated with decreases in renal angiotensin-converting enzyme activity and/or blood pressure in diabetic mice. C57Bl/6 mice were injected with streptozotocin (200 mg/kg, i.v.) and randomized to receive either imidapril (1 and 5 mg/kg) or captopril (10 and 50 mg/kg) or vehicle by gavage for 28 days. Each assay was performed on 8-10 mice from each treatment. At 28 days after the start of drug treatment, imidapril and captopril significantly reduced blood pressure of the diabetic mice, and this effect of captopril was stronger than that of imidapril. On the other hand, inhibition of renal angiotensin-converting enzyme activity by imidapril was stronger than that by captopril. Imidapril and captopril dose-dependently inhibited urinary albumin excretion to similar extents, but they failed to inhibit the renal hypertrophy and elevation of creatinine clearance. Total renal angiotensin-converting enzyme activity was significantly reduced in diabetic mice, but immunohistochemical localization of angiotensin-converting enzyme was intensive in the vasculature and glomeruli of the diabetic kidney. In conclusion, both effects on blood pressure and angiotensin-converting enzyme activity may be involved in the prevention of development of diabetic nephropathy by imidapril and captopril in streptozotocin-induced diabetic mice. The data suggest that the degrees of contribution of their effects on blood pressure and renal angiotensin-converting enzyme activity to the inhibition of urinary albumin excretion may be different between the two angiotensin-converting enzyme inhibitors.

Albuminuria↗

Low density lipoprotein receptor-related protein gene polymorphisms and risk for late-onset Alzheimer's disease in a Japanese population.

Low density lipoprotein (LDL) receptor-related protein (LRP) gene polymorphisms located in the 5' region and in exon 3, and the apolipoprotein E (APOE) genotype were determined in 100 Japanese patients affected by late-onset Alzheimer's disease (AD). We matched 246 controls for age and found no association between the polymorphism located in the 5' region of the LRP gene. The distribution of LRP exon 3 genotypes and alleles did not differ between AD and the control groups. However, the frequency of T allele in the Alzheimer's group having APOE-epsilon4 was lower than that in the control group having APOE-epsilon4, but it was only marginally significant (p = 0.022). Age of onset was significantly younger in the patients with CC genotype than those carrying the T allele (p = 0.03), and this trend was more evident among non-APOE-epsilon4 carriers (p = 0.008). These results support the possibility that ApoE and LRP may contribute to the development of AD.

Age of Onset↗

Myotonic dystrophy associated with 47 XYY syndrome.

A case of myotonic dystrophy with 47 XYY presented with tall stature and mental retardation. The patient was a 37-year-old male. In addition to grip myotonia and percussion myotonia, severe weakness and atrophy were noted in the face and the neck muscles and in the distal muscles of the four limbs. He also had diabetes mellitus, cataracts and sexual behavior abnormalities. He was found to be 47 XYY from chromosomal examinations. The combination of 47 XYY syndrome and myotonic dystrophy has not been reported previously.

Adult↗

Comparison of outer membrane protein genes omp and pmp in the whole genome sequences of Chlamydia pneumoniae isolates from Japan and the United States.

Chlamydia pneumoniae is a widespread pathogen of the respiratory tract that is also associated with atherosclerosis. The whole genome sequence was determined for a Japanese isolate, C. pneumoniae strain J138. The sequence predicted a variety of genes encoding outer membrane proteins (OMPs) including ompA and porB, another 10 predicted omp genes, and 27 pmp genes. All were detected in the whole genome sequence of strain CWL029, a strain isolated and sequenced in the United States. A comparative study of the OMPs of the two strains revealed a nucleotide sequence identity of 89.6%-100% (deduced amino acid sequence identity, 71.1%-100%). The overall genomic organization and location of genes are identical in both strains. Thus, a few unique sequences of the OMPs may be essential for specific attributes that define the differential biology of two C. pneumoniae strains.

Bacterial Outer Membrane Proteins↗

An association study between alcoholism and the serotonergic receptor genes.

BACKGROUND: Linkage and association studies of alcoholism using DNA makers have been conducted without conclusive results. The comorbidity of alcoholism with affective disorder indicates that dysfunction of the serotonergic system may play an important role in developing alcoholism. METHODS: We studied the genetic association between alcoholism and alleles of the HTR1A, HTR2A, and HTR2C genes. The subjects were 91 biologically unrelated alcoholics and 90 controls. Polymorphisms of these genes were determined by polymerase chain reaction restriction fragment length polymorphisms, and the data were analyzed by chi2 tests. RESULTS: We found no significant association between alcoholism and the HTR1A, HTR2A, and HTR2C genes. CONCLUSIONS: The study results suggest that these serotonergic receptor genes may not directly contribute to the etiology of alcoholism.

Adult↗

Two cases of HLA-DR2-negative hypersomnia manifesting sleep-onset rapid eye movement periods in the multiple sleep latency test.

We encountered two cases expressing excessive daytime sleepiness (EDS) and manifesting two or more sleep-onset rapid eye movement (REM) periods in the multiple sleep latency test. Unbearable daytime sleepiness occurred abruptly, which usually led to short-lasting naps, after which the patients felt refreshed. The EDS was successfully reduced by treatment with methylphenidate. In spite of these features similar to narcolepsy, these cases of REM hypersomnia did not present cataplexy or other auxiliary symptoms of narcolepsy, and, furthermore, the class-II human leukocyte antigen DR2 appeared to be negative.

Adult↗

Paracoccus carotinifaciens sp. nov., a new aerobic gram-negative astaxanthin-producing bacterium.

The strain E-396T, isolated from soil, was Gram-negative, aerobic, orange-pigmented, rod-shaped, motile by peritrichous flagella and astaxanthin-producing. This organism produced carotenoids, mainly astaxanthin, and did not produce bacteriochlorophyll. The ubiquinone system was Q-10. Analysis of the 16S rRNA sequence of strain E-396T showed it to be a member of the alpha-3 subclass of the Proteobacteria, forming a cluster with the species of the genus Paracoccus. On the basis of the production of orange pigments and motility by peritrichous flagella, together with DNA-DNA reassociation data, it is concluded that the new isolate should be classified into a new species of the genus Paracoccus, Paracoccus carotinifaciens sp. nov. The type strain is E-396T (= IFO 16121T).

Base Sequence↗

Involvement of angiotensin II in development of spontaneous nephrosis in Dahl salt-sensitive rats.

We investigated the effect of angiotensin-converting enzyme inhibition on spontaneous nephrosis in Dahl salt-sensitive (Dahl/S) rats. Dahl/S rats fed on a normal sodium diet spontaneously developed nephrosis and mild hypertension from a young age. In young Dahl/S rats, an angiotensin-converting enzyme inhibitor, imidapril, attenuated the development of proteinuria accompanied by a decrease in blood pressure. Methylprednisolone, a potent therapeutic agent for proteinuria, did not affect the development of nephrosis. An angiotensin AT1 receptor antagonist, losartan, but not a Ca2+ channel blocker, verapamil, inhibited the development of nephrosis while both agents decreased blood pressure to a similar extent as imidapril. In mature Dahl/S rats, imidapril suppressed not only the development of proteinuria but also the glomerular lesions. It is concluded that the development of spontaneous nephrosis in Dahl/S rats is mediated by angiotensin II.

Aging↗

Enhancement of slow-wave sleep by tumor necrosis factor-alpha is mediated by cyclooxygenase-2 in rats.

Tumor necrosis factor-alpha (TNFalpha) was infused into the subarachnoid space of the rat rostral basal forebrain, which was previously defined as a prostaglandin (PG) D2-sensitive, sleep-promoting zone. TNFalpha increased the amount of slow-wave sleep (SWS), decreased that of paradoxical sleep (PS), and caused fever and anorexia. The TNFalpha-induced SWS enhancement, fever and anorexia were all blocked by co-infusion of diclofenac, a non-selective cyclooxygenase (COX) inhibitor, and by pretreatment with NS-398, a COX-2-specific inhibitor. In striking contrast, the TNFalpha-induced suppression of PS was not affected by the inhibitors. These results indicate that COX-2-mediated hyperproduction of PGs is critically involved in the enhancement of SWS, fever, and anorexia but not in the suppression of PS, caused by TNFalpha infused into the PGD2-sensitive zone.

Animals↗

Angiotensin II maintains the structure and function of glomerular mesangium via type 1a receptor. What we have learned from null mutant mice minus the angiotensin II type 1a receptor gene.

The angiotensin II type 1a (AT1a) receptor is the major receptor effecting the multiple actions of angiotensin II on the cardiovascular system. It is expressed abundantly in the glomerular mesangial cells of the kidney. We investigated glomerular changes in null mutant mice minus the AT1a receptor gene to gain an understanding of the in vivo action of angiotensin II via AT1a on the mesangium. Morphological observations and morphometric analysis revealed that the glomerular volume was greatly increased owing to the expansion of the mesangial area, which contained fluid-filled spaces with a small amount of fibrillar components. The mesangial cells lost contact with each other and with the perimesangial area of the glomerular basement membrane (GBM), so that the glomerular capillary neck was greatly widened. These findings suggest a defect of the anchoring function of mesangial cells resulting from some abnormality in mesangial matrix formation. We conclude that angiotensin II has an important role in the structural and functional maintenance of the mesangium via the AT1a receptor, especially by reinforcing the connection between mesangial cells and GBM via the mesangial matrix.

Angiotensin II↗