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Biomedical subjects

T Shiomi

Publications and source records attributed to T Shiomi.

At least 73 records · Page 4Linked to original sources

A novel benzodiazepine inverse agonist, S-8510, as a cognitive enhancer.

1. Pharmacological actions of a novel benzodiazepine receptor ligand, S-8510 (2-(3-isoxazolyl)-3,6,7,9-tetrahydroimidazo[4,5-d]pyrano+ ++[4,3-b] pyridine monophosphate monohydrate), were examined in in vitro and in vivo studies. 2. S-8510 was characterized as a partial inverse agonist with a modest GABA ratio and low efficacy. 3. S-8510 ameliorated memory impairment induced by cholinergic deficit in the water maze paradigm of Wistar rats. 4. S-8510 augmented LTP of the Schaffer collateral/commissural fiber-CA1 synapses in the hippocampal slice preparations of SD rat. 5. S-8510 increased the extracellular levels of acetylcholine and noradrenaline in the hippocampus of Wistar rat. 6. S-8510 selectively potentiated pentylenetetrazol-induced convulsion without affecting minimal electroconvulsive shock- or strychnine-induced convulsion in ddY mice. 7. S-8510 failed to induce any sign of anxiety in the Wistar rat pro-conflict test. 8. S-8510 showed antidepressant-like pharmacological actions in ddY mice. 9. These results suggest that S-8510 can be used as a therapeutic drug for senile dementia, including Alzheimer's disease with little risk for inducing anxiety or convulsion.

Animals↗

Retrospective study on the usefulness of radius and lumbar bone density in the separation of hemodialysis patients with fractures from those without fractures.

We measured bone mineral density (BMD) at the lumbar spine (LS-BMD), 1/3 radius (1/3R-BMD), and ultradistal radius (UDR-BMD) in 59 men (4 with spine fractures and 4 with nonspine fractures) and 65 women (10 with spine fractures and 9 with nonspine fractures), all receiving maintenance hemodialysis (HD). The BMD at each site expressed absolutely in g/cm2 was significantly lower in women than in men (p = 0.0001). In men, the absolute and age-matched values of both 1/3R- and UDR-BMD were inversely and significantly correlated with the duration of HD, and with serum alkaline phosphatase and parathyroid hormone levels (p < 0.05), whereas such relationships were obscure in women. On the other hand, the absolute values of BMD at each site in women but not in men were inversely and significantly correlated with patient age (p < 0.001). In both sexes, R-BMD was significantly lower in both the spine and nonspine fracture groups than in the nonfracture group (p < 0.05 and p < 0.01, respectively), whereas the only significant difference in LS-BMD was that it was lower in women with spine fractures than in women without fractures, when expressed as its absolute value (p < 0.05). By receiver operating characteristic analyses, both the absolute and age-matched values of R-BMD were better than LS-BMD as a determinant of non-spine fracture histories, and were similar to absolute LS-BMD as a determinant of spine fracture histories. We conclude that R-BMD is more valuable than LS-BMD for discriminating HD patients with all types of fractures from those without fractures.

Adult↗

Urethral opening pressure in patients with myelodysplasia.

We evaluated 60 patients with myelodysplasia using the urethral opening pressure (UOP) which is defined as the total intravesical pressure at the moment when urine passes through the external sphincter by the Credé or the Valsalva maneuver. Twenty nine of the patients showed UOP value greater than 35 cmH2O and 31 below 35 cmH2O. In the high pressure group, patients showed a tendency to preserve sphincter activity and had mild paralysis of the lower extremities. In contrast, most of patients in the low pressure group showed an underactive sphincter and severe paralysis of the lower extremities. The incidence of deterioration of the upper urinary tract, vesicoureteral reflux (VUR) and bladder deformity were significantly high in the high pressure group than those in the low pressure group (75.9% vs 16.1%, 72.4% vs 22.6%, 82.8% vs 29.0%, respectively, P < 0.05). During the follow-up period (42 months on average), the voiding methods were changed in 15 patients from the Credé maneuver to clean intermittent catheterization, and total of 12 operations were performed (10 antiVUR operation and two with an ileocystoplasty). Finally, approximately 90% of the patients in both the high and the low pressure groups were evaluated as improved or stable in the upper urinary tract, VUR and bladder deformity after conservative or surgical managements. UOP is considered to be one of the useful parameters to select the high risk patient in the urological management of myelodysplastic patients.

Adolescent↗

Augmented very low frequency component of heart rate variability during obstructive sleep apnea.

After documenting the presence of obstructive sleep apnea syndrome (OSAS) through polysomnographic monitoring, we performed simultaneous ambulatory recordings of electrocardiogram, oronasal airflow, and pulse oximetry on 12 OSAS patients with normal autonomic nervous function for a period of 24 hours. The power spectrum of heart rate variability was investigated before and during treatments using dental appliances. Freuquency domain analysis showed that the very low frequency component of heart rate (0.008-0.04 Hz) was increased in OSAS patients and that a very low frequency peak appeared during episodes of obstructive sleep apnea. The increase in very low frequency identification was synchronized with episodes of absence of air exchange or hypoxemia (decreased arterial oxygen saturation) that occurred repeatedly at a cycle length of 25-120 seconds in our subjects. Frequency domain analysis of heart rate variability before and during prosthetic mandibular advancement treatment showed that only the very low frequency was significantly decreased during prosthetic mandibular advancement treatment, whereas the other frequencies, i.e. high, low, and ultralow frequency component values, showed no significant changes. Time domain analysis of heart rate variability before and during prosthetic mandibular advancement treatment showed no significant changes in any of these parameters. Frequency domain analysis of heart rate variability during nocturnal sleep, especially investigation of very low frequency and very low frequency peak, can be a noninvasive low-cost approach to diagnose and even better monitor subjects undergoing treatment at home, particularly considering that R-R intervals can be extracted from pulse oximetry and that analysis software programs are already commercially available.

Adult↗

Blood pressure "dipping" and "non-dipping" in obstructive sleep apnea syndrome patients.

Obstructive sleep apnea syndrome (OSAS) has been associated with a higher than normal cardiovascular morbidity and mortality. Some OSAS patients lack the sleep-related, nocturnal decrease, or "dip," in blood pressure which is seen in normal individuals. These subjects, called "non-dippers," may be at greater risk for cardiovascular problems. We studied 40 OSAS patients (including 3 women) and 6 control subjects, all identified by polysomnography, for nocturnal blood pressure "dipping." We performed a second nocturnal polysomnogram to determine their apnea and hypopnea indices, (A + H)I, and oxygen saturation levels at the beginning of the study and then initiated 48 hours of ambulatory blood pressure monitoring, with data points collected every 30 minutes. Controls, which included one hypertensive subject, were all dippers. Nineteen OSAS subjects (48% of OSAS individuals) were systolic non-dippers and only 9 of them (22.5%) were diastolic non-dippers. We considered the following clinical variables as potential predictors of non-dipping: age, body mass index, respiratory disturbance index, years of reported loud snoring by bed partners, lowest oxygen saturation during nocturnal sleep, and percentage of sleep time spent with oxygen saturation below 90%. Multiple regression analyses indicated respiratory disturbance index as the only significant variable for systolic (p = 0.04) and diastolic (p = 0.03) blood pressure non-dipping. When we forced the following two nonsignificant variables into the model, they showed a very meager impact: number of years with reported loud snoring (p = 0.4 and p = 0.5, respectively for systolic and diastolic blood pressure non-dipping) and age (p = 0.5 and p = 0.6). The calculated model explained only a low percentage of the variance with an r2 of 0.25 and 0.26 for systolic and diastolic blood pressure non-dipping, respectively. Analysis of hypertension/normotension and dipping/non-dipping failed to show a significant relationship in the studied population. Fifty percent of the normotensive OSAS subjects were non-dippers and 43% of the hypertensive OSAS subjects were also non-dippers. We found a relationship between increasing respiratory disturbance index and increasing average 24-hour systolic blood pressure only when OSAS subjects were non-dippers and hypertensive.

Adult↗

Current status of antihypertensive therapy for elderly patients in Japan.

To assess how elderly Japanese hypertensive patients are treated by specialists, we conducted a cross-sectional survey. A total of 1,163 outpatients aged 50 years or older were studied. Hypertension was diagnosed in 939 of these patients, and 827 were receiving drug therapy. The average blood pressure during therapy was 143 +/- 16/81 +/- 10 mmHg. In patients aged 70 years or older, systolic blood pressure during antihypertensive therapy was significantly higher (p < 0.01) and diastolic blood pressure was significantly lower (p < 0.01) than the corresponding values in those aged 50 to 59 years or 60 to 69 years. The calculated mean blood pressures were similar in the different age groups. The rate of monotherapy in the patients aged 70 years or older was 58.8%, which was significantly higher (p < 0.01) than the rates of monotherapy in the other age groups. Calcium channel blockers were prescribed in about 80% of patients, irrespective of age or comorbidity. Of the patients receiving calcium channel blockers, 43.5% were treated with monotherapy. This rate significantly (p < 0.01) increased with advancing age. Diastolic blood pressures were significantly lower (p < 0.05) in patients with stroke and in those with ischemic heart disease, diabetes mellitus, or dyslipidemia, as compared with patients with no comorbidity. Among patients aged 70 years or older, the difference in systolic blood pressure between those with ischemic heart disease and those with no comorbidity was not significant. Blood pressure in elderly hypertensive patients was reduced to a level similar to that in younger patients. The target blood pressure was influenced by the presence of comorbidity. Furthermore, specialists showed a high preference for the use of calcium channel blockers in the management of hypertension.

Activities of Daily Living↗

Upper airway resistance syndrome, nocturnal blood pressure monitoring, and borderline hypertension.

Upper airway resistance syndrome (UARS) is a sleep-disordered breathing syndrome characterized by complaints of daytime fatigue and/or sleepiness, increased upper airway resistance during sleep, frequent transient arousals, and no significant hypoxemia. Of a population of 110 subjects (58 men) diagnosed as having UARS, we investigated acute systolic and diastolic BP changes seen during sleep in two different samples. First, six patients from the original subject pool were found to have untreated chronic borderline high BP, and were subjected to 48 h of continuous ambulatory BP monitoring before treatment and another 48 h of BP monitoring 1 month after the start of nasal-continuous positive airway pressure (N-CPAP) treatment. Five of six subjects used their equipment on a regular basis and had their chronic borderline high BP completely controlled. No change in BP values was seen in the last subject, who discontinued N-CPAP after 3 days. A second protocol investigated seven normotensive subjects drawn from the initial subject pool. Continuous radial artery BP recording was performed during nocturnal sleep with simultaneous polygraphic recording of sleep/wake variables and respiration. BP changes were studied during periods of increased respiratory efforts and at the time of alpha EEG arousals. Increases in systolic and diastolic BP were noted during the breaths with the greatest inspiratory efforts without significant hypoxemia. A further increase in BP was noted in association with arousals. Three of these subjects also underwent echocardiography during sleep, which demonstrated a leftward shift of the interventricular septum with pulsus paradoxus in association with peak end-inspiratory esophageal pressure more negative than -35 cm H2O. Our study indicates that, in the absence of classic apneas, hypopneas, and repetitive significant drops in oxygen saturation (below 90%), repetitive increases in BP can occur as a result of increased airway resistance during sleep. It also shows that, in some patients with both UARS and borderline high BP, high BP can be controlled with treatment of UARS. We conclude that abnormal upper airway resistance during sleep, often associated with snoring, can play a role in the development of hypertension.

Adult↗

Isolation of human purH gene expressed in the rodent transformant cells by subtractive enrichment of 3'-untranslated region of human transcript.

A subtraction procedure was developed for identification and isolation of a human gene transcribed in mouse transformant cells. The procedure was based on subtractive enrichment of the products that were amplified by the combination of reverse transcription and polymerase chain reaction from the 3'-untranslated region (3'-UTR) of human poly(A)+ RNA expressed in the mouse transformant cells. To assess the ability and usefulness of the procedure, we attempted to recover the human purH gene from a mouse transformant cell line, which was originally established by functional complementation using the human metaphase chromosome-mediated gene transfer technique from a mouse purH-negative mutant cell line. Using our procedure, a part of the human transcript in the transformant cells was successfully identified and isolated. The full-length cDNA was isolated using the 3'-UTR clone as a probe, and its biological activity was confirmed by introducing it into the mouse purH-negative mutant cells.

Acyltransferases↗

Complementary DNA sequence and chromosomal localization of xpg, the mouse counterpart of human repair gene XPG/ERCC5.

We have molecularly cloned and sequenced the mouse counterpart of the human repair gene XPG/ERCC5 cDNA. The mouse xpg cDNA had a single long open reading frame predicted to encode 1170 amino acid residues (predicted M(r) of 130,753). Northern blot analysis has been carried out to determine the size and tissue transcription specificity of the mouse xpg mRNA. The xpg gene expressed one species of transcript with 4.3 kb at similar levels in five mouse tissues examined. We have determined the chromosomal location of the xpg gene by both in situ hybridization and molecular linkage analysis. The xpg gene was localized at 2.3 cM proximal to the microsatellite locus D1Mit18 on the R-positive B band of mouse chromosome 1. By in situ hybridization with the mouse xpg probe, the rat homolog of the mouse xpg was localized on q22.3 band of rat chromosome 9, which has been known to have a conserved linkage homology to mouse chromosome 1. In the case of human, the XPG/ERCC5 gene has been reported to be assigned to human chromosome 13q32.3-q33.1, where any conserved linkage homology to mouse chromosome 1 has not been found so far. Thus, these results show new regions of conserved linkage homology among mouse chromosome 1, rat chromosome 9, and human chromosome 13q.

Amino Acid Sequence↗

[Evaluation of sexual function in adults with myelomeningocele].

In the present study, sexual function in 46 patients (22 males and 24 females) with myelomeningocele was assessed by a questionnaire study. The mean age of the patients was 24.0 +/- 9.6 years (with an age range of 18 to 50) for male patients and 25.2 +/- 6.2 years (with an age range of 18 to 42) for female patients. Having interest in the opposite sex and sexual desire were evident in 95% and 100% of male patients, and 83% and 75% of female patients, respectively. In male patients, erection was achieved in 95% by visual stimulation and in 86% by tactile stimulation. However, only 27% of the patients with erectility were satisfied with penile rigidity. Ejaculation and orgasm was noted in 67%. Orgasm was frequently seen in patients whose external sphincter activity was maintained. The age and the degree of lower extremity paralysis according to Sharrard classification were not significantly correlated with sexual function. In female patients, menstruation was regular in 95%, vaginal secrete was adequate in 88%, but only 19% of the patients felt ecstacy around perineal lesion at coital movements. In female patients, sexual function was not correlated with the age, the degree of lower extremity paralysis and detrusor activity-sphincter activity. Although most patients had sexual desire, only 18% of the males, and 33% of the females, had sexual intercourse activities. It appears, therefore, that these patients need to be given appropriate advice.

Adolescent↗

An ERCC5 gene with homology to yeast RAD2 is involved in group G xeroderma pigmentosum.

We have isolated a human excision repair gene ERCC5 which complements the defect of the mouse UV-sensitive mutant XL216 (rodent complementation group 5). Here we report cDNA cloning of human and mouse ERCC5 genes using an exon containing an ERCC5 fragment as a probe. The ERCC5 cDNA encodes a predicted 133-kDa nuclear protein that shares some homology with the product of the yeast DNA repair gene RAD2. Transfection with mouse ERCC5 cDNA restored normal levels of UV resistance to XL216 cells. Microinjection of ERCC5 cDNA specifically restored the defect of xeroderma pigmentosum group G cells (XP-G) as measured by unscheduled DNA synthesis, and XP-G cells stably transformed with ERCC5 cDNA showed nearly normal UV resistance.

Amino Acid Sequence↗

Arrhythmias in centenarians.

BACKGROUND: Many studies have shown an increase in the prevalence of arrhythmias with advancing age. However, little is known about arrhythmias in centenarians. METHOD AND RESULTS: Thirty-two Japanese centenarians aged 100-106 years (14 males, 18 females) were studied. All of them had 12-lead ECGs, and 22 also had 24-hour ambulatory monitoring. As controls, 89 healthy Japanese elderly from the same geographic area underwent 12-lead ECG. Their mean age was 75 +/- 6 years with a range of 63-93 years, and there were 28 males and 61 females. Twenty-three of them also had Holter ECGs. On the 12-lead ECG, the heart rate was slightly, but significantly, higher in the centenarians (76.8 +/- 12.7 beats/min) than that in the elderly subjects (74.9 +/- 5.9 beats/min, P < 0.005). PQ and QTc were significantly longer in the centenarians (174 +/- 29 and 439 +/- 33 msec, respectively) compared with the elderly subjects (158 +/- 23 and 417 +/- 31 msec, P < 0.005 and P < 0.001, respectively). Supraventricular premature beats (SVPBs) were observed in 31% of the centenarians and in 4% of the elderly subjects (P < 0.001). First- and second-degree AV block was recorded in 25% of the centenarians and 1% of the elderly subjects (P < 0.001). Right bundle branch block was found in 19% of the centenarians and 7% of the elderly subjects (P < 0.05). There were no differences in the frequency of ventricular premature beats (VPBs) or QRS voltage. On the Holter ECG, there were no significant differences in average heart rate, maximum heart rate, minimum heart rate, or the longest RR interval. A subgroup of centenarians had frequent SVPBs. However, none of them had > 1,000 VPBs/day as opposed to four elderly subjects (P < 0.01). Atrial fibrillation was not observed in any records of the centenarians despite the presence of frequent SVPBs. CONCLUSION: These data suggest that conduction disturbances of the AV nodal--His-Purkinje system and frequent SVPBs are common in centenarians, whereas very frequent VPBs and atrial fibrillation seem less common.

Age Factors↗

Characterization of the formae speciales of Fusarium oxysporum causing wilts of cucurbits by DNA fingerprinting with nuclear repetitive DNA sequences.

The genetic relatedness of five formae speciales of Fusarium oxysporum causing wilts of cucurbit plants was determined by DNA fingerprinting with the moderately repetitive DNA sequences FOLR1 to FOLR4. The four FOLR clones were chosen from a genomic library made from F. oxysporum f. sp. lagenariae 03-05118. Total DNAs from 50 strains representing five cucurbit-infecting formae speciales, cucumerinum, melonis, lagenariae, niveum, and momordicae, and 6 strains of formae speciales pathogenic to other plants were digested with EcoRV and hybridized with 32P-labeled FOLR probes. The strains were clearly distinguishable at the formae specialis level on the basis of FOLR DNA fingerprints. Fifty-two fingerprint types were detected among the 56 strains by using all FOLR probes. These probes were used to infer phylogenetic relationships among the DNA fingerprint types by the unweighted pair group method using averages and parsimony analysis. The fingerprint types detected in each of the formae speciales cucumerinum, lagenariae, niveum, and momordicae were grouped into a single cluster. However, two different genetic groups occurred in the formae specialis melonis. The two groups also differed in pathogenicity: one group caused wilts of muskmelon and oriental melon, while the second was pathogenic only to muskmelon. The fingerprint types of different formae speciales pathogenic to plants other than cucurbits were distinguishable from one another and from the fingerprints of the cucurbit-infecting strains. These results suggest that the cucurbit-infecting formae speciales are intraspecific variants distinguishable at the DNA level and in their host range.

Cloning, Molecular↗

Pharmacological studies on a new dihydrothienopyridine calcium antagonist, S-312-d. 5th communication: anticonvulsant effects in mice.

S-312, S-312-d, but not S-312-l, L-type calcium channel antagonists, showed anticonvulsant effects on the audiogenic tonic convulsions in DBA/2 mice; and their ED50 values were 18.4 (12.8-27.1) mg/kg, p.o. and 15.0 (10.2-23.7) mg/kg, p.o., respectively, while that of flunarizine was 34.0 (26.0-44.8) mg/kg, p.o. Although moderate anticonvulsant effects of S-312-d in higher doses were observed against the clonic convulsions induced by pentylenetetrazole (85 mg/kg, s.c.) or bemegride (40 mg/kg, s.c.), no effects were observed in convulsions induced by N-methyl-D-aspartate, picrotoxin, or electroshock in Slc:ddY mice. S-312-d may be useful in the therapy of certain types of human epilepsy.

Administration, Oral↗

[Urethral opening pressure as a parameter for introduction of the proper voiding modality in myelodysplastic patients].

To introduce the proper voiding modality to patients with myelodysplasty, urethral opening pressure (UOP), an intravesical pressure just at the beginning urine flows out beyond the external urethral sphincter, was measured in 63 myelodysplastic patients. Among 45 renal units with any morphological or functional changes at the first UOP measurement, 37 units (82.2%) were included in the high UOP group (> or = 35 cmH2O). And among 41 ureters with VUR of more than grade 2, 32 (78.0%) were in the high UOP group. In addition, deformity of the urinary bladder was observed in 36 patients, and 26 (72.2%) of these bladders showed high UOP values. Therefore, all the patients could be divided into two groups: high UOP group (> or = 35 cmH2O, 28 cases) and low UOP group (< 35 cmH2O, 35 cases). Twenty-three patients (82.1%) with high UOP values had been mainly treated with clean intermittent catheterization (CIC). In contrast, 24 patients (68.6%) with low UOP values had been allowed to urinate by Credè' or Valsalva's method. In the followup study for 40 to 44 months, patients in the CIC group obtained good prognosis as for morphological or functional changes of the urinary tract. On the other hand, patients in the Credè' or Valsalva's method group showed a significantly higher deterioration rate in the high UOP group (80.0%) than that in the low UOP group (9.1%) (p < 0.005). From these results, hopely that in myelodysplastic patients with the underactive detrusor, CIC may be introduced for low pressure voiding to those who show high UOP values as early as possible. On the other hand, those who show low UOP values may be managed with Credè' or Valsalva's method as well as CIC. Thus, UOP is considered a possible prognostic factor for the morphological and functional changes of the urinary tract, which may be a useful parameter in decision of voiding modalities in myelodysplastic patients.

Adolescent↗

Effects of different patterns of stairclimbing on physiological cost and motor efficiency.

The purpose of the present study was to investigate the effects of different motion patterns of ascending and descending stairs on oxygen consumption (VO2), heart rate (HR) and efficiency. Five healthy males performed ascending and descending by two motion patterns; climbing foot over foot (usual climb) and climbing with both feet on each step (stepping climb), at the stepping rates of 25, 37, 50, and 62 steps.min-1. The results showed that VO2 and HR were significantly higher (on average 10%) with the stepping climb than the usual climb, and the difference between them tended to increase in proportion to the stepping rates. HR values to VO2 in the stepping climb significantly higher than those in the usual climb at each stepping rate during stair ascent and descent. In terms of motor efficiency and efficiency of locomotion (kcal.step-1.kg-1) the usual climb was more efficient than the stepping climb during stair descent and ascent. These results suggested that usual climb has the advantages of lower physiological cost and higher efficiency than the stepping climb with increasing the stepping rate. Furthermore, the effects of motion patterns during stair descent were less than those during ascent.

Adult↗

[Evaluation of plasma prothrombin fragment 1+2 in healthy donors and thrombotic diseases].

We have evaluated plasma F1+2 values by enzyme immunoassay (Enzygnost F1+2; Behringwerke) in 80 healthy blood donors in various ages and compared to that from patients with DIC, thrombosis and oral anticoagulant therapy. The reference range of F1+2 from 35 donors with 20 to 29 age-group, was found 0.82 +/- 0.39 nM, whereas the range from 20 donors with 30 to 39 age-group showed higher F1+2 levels with 1.46 +/- 0.56nM (p < 0.001). F1+2 values from 15 donors with 40 to 49 age-group revealed similar with 30 to 39 age-group, while the range from 10 donors with 50 to 59 age-group was found much higher F1+2 levels with 2.16 +/- 0.80nM (p < 0.001). In patients with DIC, F1+2 levels were significantly higher than those in all healthy subjects (p < 0.01). In patients under stable oral anticoagulant therapy, F1+2 values were significantly lower than in healthy donors with any age-group (p < 0.001). On the contrary, in patients with thrombosis including 9 AMI and 4 DVT, the determination of F1+2 values appeared controversial. They were significantly higher than those in 20 age-group donors (p < 0.001), however, when compared with those in all healthy donors, it showed no statistical significance. These results suggest that evaluation of reference range of plasma F1+2 values is very important from the viewpoint of aging. In addition, F1+2 determination is clinically useful for monitoring of DIC and anticoagulant therapy.

Adult↗