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Biomedical subjects

R Sakakibara

Publications and source records attributed to R Sakakibara.

At least 37 records · Page 2Linked to original sources
PubMed2003

Effects of subthalamic nucleus stimulation on the micturation reflex in cats.

High frequency stimulation (HFS) of the subthalamic nucleus (STN) has been performed to reverse motor dysfunction in severe parkinsonian patients. Recent studies suggested that neural circuitry in the basal ganglia might regulate micturition function as well. In 15 adult male cats under ketamine anesthesia, in which spontaneous isovolumetric micturition reflex had been generated, we performed electrical stimulation and extracellular single unit recording in the STN. Electrical stimulation applied in the STN elicited inhibition of the micturition reflex. None of the responses was facilitatory. Effective amplitude of the electrical stimulation for evoking inhibitory responses was less than 50 microA, which gradually increased and exceeded 250 microA as the location of the stimulation exceeded an area of the STN. Effective frequency of the electrical stimulation with given stimulus intensity was 50 Hz and higher. Total 10 neurons were recorded in the STN that were related to urinary storage/micturition cycles. All neurons were tonically active throughout storage/micturition cycles with storage phase predominance, with almost constant firing activities during the storage phase. In conclusion, our results showed that HFS-STN inhibited the micturition reflex and there were micturition-related neuronal firings in the STN in cats, suggesting the STN may be involved in neural control of micturition. The results also provide an implication that clinical HFS-STN may alter urinary function in parkinsonian patients.

Animals↗
PubMed2003

Colonic transit time and rectoanal videomanometry in Parkinson's disease.

BACKGROUND: Constipation is a prominent lower gastrointestinal tract dysfunction that occurs frequently in Parkinson's disease (PD). OBJECTIVE: To investigate colonic transport and dynamic rectoanal behaviour during filling and defecation in patients with PD. METHODS: Colonic transit time (CTT) and rectoanal videomanometry analyses were performed in 12 patients with PD (10 men and 2 women; mean age, 68 years, mean duration of disease, five years; mean Hoehn and Yahr grade, 3; decreased stool frequency (<3 times a week) in six, difficulty in stool expulsion in eight) and 10 age matched normal control subjects (7 men and 3 women; mean age, 62 years; decreased stool frequency in two, difficulty in stool expulsion in two). RESULTS: In the PD patients, CTT was significantly prolonged in the rectosigmoid segment (p<0.05) and total colon (p<0.01) compared with the control subjects. At the resting state, anal closure and squeeze pressures of PD patients were lower than those in control subjects, though not statistically significant. However, the PD patients showed a smaller increase in abdominal pressure on coughing (p<0.01) and straining (p<0.01). The sphincter motor unit potentials of the patients were normal. During filling, PD patients showed normal rectal volumes at first sensation and maximum desire to defecate, and normal rectal compliance. However, they showed smaller amplitude in phasic rectal contraction (p<0.05), which was accompanied by an increase in anal pressure that normally decreased, together with leaking in two patients. During defecation, most PD patients could not defecate completely with larger post-defecation residuals (p<0.01). PD patients had weak abdominal strain and smaller rectal contraction on defecation than those in control subjects, though these differences were not statistically significant. However, the PD patients had larger anal contraction on defecation (p<0.05), evidence of paradoxical sphincter contraction on defecation (PSD). CONCLUSIONS: Slow colonic transit, decreased phasic rectal contraction, weak abdominal strain, and PSD were all features in our PD patients with frequent constipation.

Adult↗
PubMed2001

Questionnaire-based assessment of pelvic organ dysfunction in Parkinson's disease.

Although patients with Parkinson's disease (PD) experience pelvic organ dysfunction of the urinary bladder, bowel and genital organs, an accurate incidence of the dysfunction and its characteristics have yet to be ascertained. We devised a detailed questionnaire on these three pelvic organ functions in PD patients and control subjects, in our search for a hallmark that would distinguish between the two groups. The PD group comprised 115 patients; 52 men and 63 women, age range 35-69 (average 59) years old, average duration of illness 6 years, median Hoehn and Yahr stage 3. All were taking levodopa with/without dopamine agonists. The control group comprised 391 local individuals who were undergoing an annual health survey; 271 men and 120 women, age range 30-69 (average 48) years old. The questionnaire had three parts: bladder (nine questions), bowel (four questions), and sexual (three questions for women, five for men) function. Each question was scored from 0 (none) to 3 (severe) with an additional quality of life (QOL) index scored from 0 (satisfied) to 3 (extremely dissatisfied). The completion rate was 100% for bladder and bowel functions, whereas for sexual function, it was 95% (control) and 88% (PD) for men and 82% (control) and 60% (PD) for women. As compared with the control group, the frequency of dysfunction in the PD group was significantly higher for urinary urgency (women 42%, men 54%), daytime frequency (28%, 16%), nighttime frequency (53%, 63%), urgency incontinence (25%, 28%), retardation (44% of men), prolongation/poor stream (men 70%), straining (women 28%); constipation (63%, 69%), difficulty in expulsion (men 57%), diarrhea (men 21%); decrease in libido (84%, 83%), decrease in sexual intercourse (55%, 88%), decrease in orgasm (men 87%), and in men, decreases in erection (79%) and ejaculation (79%). The QOL index for the PD patients was significantly higher for bladder (27%, 28%) and bowel (46%, 59%) but not for sexual dysfunction, despite the group's high prevalence of sexual dysfunction. In the PD patients, fecal incontinence was associated with urinary incontinence. Stress urinary incontinence and a decrease in libido were more common in women than in men. Bladder and bowel dysfunction, but not sexual dysfunction increased with the Hoehn and Yahr stage. Sexual dysfunction, but neither bladder nor bowel dysfunction, increased with age. Patients taking levodopa and bromocriptine more frequently had bladder (voiding phase) dysfunction than those taking levodopa only. The findings show that bladder, bowel and sexual dysfunction are all prominent in patients with PD. Amelioration of pelvic organ dysfunction, particularly bowel dysfunction which most affects the quality of life, therefore should be a primary target in the treatment of patients with PD.

Adult↗
PubMed2001

SPECT imaging of the dopamine transporter with [(123)I]-beta-CIT reveals marked decline of nigrostriatal dopaminergic function in Parkinson's disease with urinary dysfunction.

We studied a correlation of urinary dysfunction with nigrostriatal dopaminergic deficit in Parkinson's disease (PD) by single-photon emission computed tomography (SPECT) imaging of dopamine transporter with [123I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (beta-CIT). Eleven patients were enrolled in the study, including four men and seven women, with a mean age of 64 years. Seven patients had urinary symptoms 1-5 years after the onset of motor disorder, which included nighttime frequency in six, urinary retardation in four, daytime frequency in one and urge urinary incontinence in one. Using a SPECT camera, the ratio specific to nondisplaceable [123I]-beta-CIT uptake, designated as "striatal V3" was obtained in the caudate, anterior and posterior putamen 24 h after the tracer injection. The striatal V3 was compared in patients with and without urinary dysfunction, and between men and women, using unpaired Student's t-test. Correlation of motor dysfunction and duration of illness with urinary dysfunction, was also analyzed. In the patients, there was a reduction of [123I]-beta-CIT binding in the striatum on both sides, particularly in the putamen contralateral to the affected body side. The striatal V3 of the caudate (p<0.01, Rt; p<0.05, Lt), anterior putamen (p<0.05, Rt) and posterior putamen (p<0.05, Rt) in patients with urinary dysfunction was significantly reduced than those without urinary dysfunction. No sex difference was seen in reduction of [123I]-beta-CIT binding. Urinary dysfunction in PD was more common in patients with higher Unified Parkinson's Disease Rating Scale (UPDRS) score, higher Hoehn-Yahr grade, but not in those with longer duration of disease, although there was no statistical significance. It is likely that our results reflect the association of urinary dysfunction and degeneration of the nigrostriatal dopaminergic cells in PD.

Aged↗
PubMed2001

Micturitional disturbance in subacute myelo-optico-neuropathy (SMON).

BACKGROUND: Micturitional disturbance is known to occur in subacute myelo-optico-neuropathy (SMON). However, its pathophysiology is uncertain and few data are available concerning urodynamic findings. We described our results of micturitional histories and urodynamic studies in patients with SMON. METHODS: A history of urinary symptoms was obtained from six patients with SMON (two men, four women; age, 49-72 years, mean 60 years; duration of illness, 14-25 years, mean 19 years). All patients underwent urodynamic studies including measurement of post-micturition residuals, urethral pressure profilometry, cystometry and simultaneous sphincter electromyography. RESULTS: All patients had micturitional symptoms including voiding symptoms in four, filling symptoms in four and urge urinary incontinence in a patient. Urodynamic studies revealed an increased maximum urethral closure pressure in two of four patients studied, decreased bladder volume at first sensation in two, detrusor hyperreflexia in three, absent bulbocavernosus reflex in a patient, and none had detrusor-sphincter dyssynergia or post-micturition residuals. Repeated urodynamic study (10 years after initial study) in a patient with detrusor hyperreflexia showed the same findings. CONCLUSION: Our results indicate that supranuclear pelvic nerve dysfunction to be mainly responsible for the micturitional disturbance in patients with SMON.

Aged↗
PubMed2001

Neurogenic failures of the external urethral sphincter closure and relaxation; a videourodynamic study.

Urinary urgency and voiding difficulty are common features in neurological diseases, which can be attributed to dysfunction of the urethral sphincter and the detrusor. However, little is known about dynamic sphincter behaviour in neurological diseases. The present study aimed at investigating neurogenic failures of the external urethral sphincter closure and relaxation by videourodynamic study. We recruited 44 neurological patients with urinary urgency and frequency, 27 men and 17 women, mean age 61 years, and 28 of them had voiding difficulty as well. None had abnormal finding of digital examination or ultrasound echography of the pelvic organs. Using triple-lumen 7F catheter under X-ray fluoroscope, we measured detrusor pressure, external urethral sphincter pressure (Pura) and external sphincter EMG in all patients. We also performed pressure-flow study and obtained the Abram-Griffiths (AG) number, a numerical grade of obstruction. During filling 30 had detrusor hyperreflexia. EMG-cystometry showed uninhibited external sphincter relaxation (UESR) in eight patients, seven of whom had detrusor hyperreflexia as well. Patients with UESR showed an abnormal reduction of Pura, mean reduction 64 +/- 27 cmH2O (mean +/- standard deviation). During UESR the Pura and EMG activity fluctuated, and fluoroscopic image showed bladder neck opening in four with extreme urge sensation, including one without detrusor hyperreflexia. During an attempt of voiding three patients with voiding difficulty had detrusor-external sphincter dyssynergia (DESD) with detrusor contraction and eight had unrelaxing external sphincter without detrusor contraction. Fluoroscopic image showed an incomplete or absent urethral opening at the external sphincter. Four of them had severe straining on voiding together with intermittent increment of EMG activity without a normal funneling of the bladder neck. The mean reduction of Pura during voiding was 6.4 +/- 6.7 cmH2O and 5.0 +/- 9.5 cmH2O (in women and men, respectively) with DESD or unrelaxing external sphincter which was less than 39 +/- 25 cmH2O and 53 +/- 47 cmH2O in those without (P < 0.01). The mean AG number was 15 +/- 21 and 51 +/- 19 (for women and men, respectively) with DESD or unrelaxing external sphincter which was larger than 6.2 +/- 34 and 35 +/- 22 in those without (P < 0.05). In conclusion, UESR and DESD/unrelaxing external sphincter could be a factor for urinary urgency and voiding difficulty in neurological patients, evidence of central dysregulation affecting the Onuf's nucleus and its fibres to the external urethral sphincter.

Adolescent↗
PubMed2001

Urinary dysfunction in Brown-Séquard syndrome.

Brown-Séquard syndrome (BS) is a rare but well documented condition of the spinal cord hemisection, comprising hemiparesis with crossed superficial sensory disturbance. However, little is known of micturitional function in BS, although some patients with BS are troubled with severe voiding difficulty and urinary incontinence. We performed urinary questionnaire and urodynamic studies in eight patients with BS, including seven men and one woman, mean age of 41 years. Detailed questionnaire showed that five of the eight patients (63%) had micturitional symptoms, including voiding difficulty in three, urinary retention in two, urinary frequency in two and urge urinary incontinence in one. Urodynamic abnormalities were noted in all five patients with micturitional symptoms, including post-micturition residuals in four (average 149 mL), high urethral closure pressure in two, increased bladder volume at first sensation in one, detrusor hyperreflexia in four, detrusor areflexia on voiding in three and unrelaxing sphincter on voiding in four. Three asymptomatic patients showed normal urodynamic finding. Micturitional symptoms were more common in patients with severe motor paresis (100%) than in those with mild motor paresis (40%), and there was no relation between micturitional disturbance with superficial or deep sensory disturbance. A combination of treatments for the underlying disorders with alpha-adrenergic blocking agent and clean, intermittent self-catheterization ameliorated the urinary dysfunction in all patients together with neurological dysfunction. In conclusion, micturitional disturbance was not uncommon in our patients with BS, particularly in those with severe motor paresis, which could ameliorate by appropriate therapies.

Adult↗
PubMed2001

Brain responses to changes in bladder volume and urge to void in healthy men.

Knowledge of how changes in bladder volume and the urge to void affect brain activity is important for understanding brain mechanisms that control urinary continence and micturition. This study used PET to evaluate brain activity associated with different levels of passive bladder filling and the urge to void. Eleven healthy male subjects (three left- and eight right-handed) aged 19-54 years were catheterized and the bladder filled retrogradely per urethra. Twelve PET scans were obtained during two repetitions of each of six bladder volumes, with the subjects rating their perception of urge to void prior to and after each scan. Increased brain activity related to increasing bladder volume was seen in the periaqueductal grey matter (PAG), in the midline pons, in the mid-cingulate cortex and bilaterally in the frontal lobe area. Increased brain activity relating to decreased urge to void was seen in a different portion of the cingulate cortex, in premotor cortex and in the hypothalamus. Both activation patterns were predominantly bilaterally symmetric and none of the effects could be attributed to the presence of the catheter. However, in some subjects, mostly those reporting intrusive sensations from the urethral catheter, there was a discrepancy between filling volume and urge so that they reported high urge with low volumes. As this 'mismatch' decreased, activation increased bilaterally in the somatosensory cortex. Our findings support the hypothesis that the PAG receives information about bladder fullness and relays this information to areas involved in the control of bladder storage. Our results also show that the network of brain regions involved in modulating the perception of the urge to void is distinct from that associated with the appreciation of bladder fullness.

Adult↗
PubMed2001

Videourodynamic and sphincter motor unit potential analyses in Parkinson's disease and multiple system atrophy.

OBJECTIVES: Urinary dysfunction is a prominent autonomic feature in Parkinson's disease (PD) and multiple system atrophy (MSA), which is not only troublesome but also a cause of morbidity in these disorders. Recent advances in investigative uroneurology offer a better insight into the underlying pathophysiology and appropriate management for urinary dysfunction. METHODS: twenty one patients with PD (15 men, six women, mean age 64 (49-76), mean disease duration 4 years (1-8 years), median Hoehn and Yahr grade 3 (1-4), all taking 300 mg/day of levodopa (100-500 mg)) and 15 with MSA (eight men, seven women, mean age 59 (48-72), mean disease duration 3 years (0.5-6 years)) were recruited. Videourodynamic and sphincter motor unit potential analyses in the patients with PD and MSA were carried out, looking for distinguishing hallmarks that might be useful in the differential diagnosis of these two diseases. RESULTS: Urinary symptoms were found in 72% of patients with PD and in 100% with MSA. Filling phase abnormalities in the videourodynamic study included detrusor hyperreflexia in 81% of patients with PD and 56% with MSA, and uninhibited external sphincter relaxation in 33% of patients with PD and 33% of those with MSA. However, open bladder neck at the start of filling was not seen in patients with PD but was present in 53% of those with MSA, suggestive of internal sphincter denervation. Sphincter motor unit potential analysis showed neurogenic motor unit potentials in 5% of patients with PD and in 93% of those with MSA, suggestive of external sphincter denervation. On voiding, detrusor-external sphincter dyssynergia was not seen in patients with PD but was present in 47% of those with MSA. Pressure-flow analysis showed that the Abrams-Griffiths number, a grading of urethral obstruction (outflow obstruction >40), in PD (40 in women and 43 in men) was larger than that in MSA (12 in women and 28 in men). Weak detrusor in PD (66% of women and 40% of men) was less common than that in MSA (71% of women and 63% of men). Postmicturition residuals >100 ml were absent in patients with PD but were present in 47% of patients with MSA. CONCLUSION: Patients with PD had less severe urinary dysfunction with little evidence of internal or external sphincter denervation, by contrast with the common findings in MSA. The findings of postmicturition residuals >100 ml, detrusor-external sphincter dyssynergia, open bladder neck at the start of bladder filling, and neurogenic sphincter motor unit potentials are highly suggestive of MSA.

Aged↗
PubMed2000

Exploring the structural basis of neurotoxicity in C(17)-polyacetylenes isolated from water hemlock.

Water hemlock, Cicuta virosa, belonging to the Umbelliferae, is well-known as a toxic plant responsible for lethal poisonings in humans as well as animals, causing tonic and clonic convulsions and respiratory paralysis. Cicutoxin (1), being a major violent toxin of the plant, is a chemical in the class of C(17)-polyacetylenes bearing a long pi-bond conjugation system, a terminal hydroxyl, and an allylic hydroxyl in its structure, and a variety of its analogues have been isolated from the plant. In the present study, various derivatives of these toxins were synthesized through acetylation, methylation, and oxidation of cicutoxin (1) and virol A (3) and B (4). 1-Dehydroxyvirol A (28) was prepared through the coupling of (7S)-dodeca-3,5-dien-1-yn-7-ol and 1-iodopentyne under Sonogashira's conditions. A monoacetylenic compound (29) was also prepared through the coupling of (5S)-1-chlorodeca-1,3-dien-5-ol and 1-iodopentyn-5-ol. The structure-activity relationships involved in the acute toxicity of cicutoxin derivatives in mice were investigated, and the length and geometry of pi-bond conjugation and the O-functional groups were found to be important for activity. The potency in inhibition of the specific binding of the noncompetitive GABA antagonist, [(3)H]EBOB, to GABA-gated Cl(-) channels of GABA receptors in rat brain cortex was found to be correlated with acute toxicity, indicating that the ability to bind to these channels plays an important role in the acute toxicity of these compounds.

Acetylene↗
PubMed2000

Comparative study of the effects of magnetic versus electrical stimulation on inhibition of detrusor overactivity.

OBJECTIVES: To perform a randomized comparative study investigating the urodynamic effects of functional magnetic stimulation (FMS) and functional electrical stimulation (FES) on the inhibition of detrusor overactivity. METHODS: Thirty-two patients with urinary incontinence due to detrusor overactivity (15 men, 17 women; age 62. 3 +/- 16.6 years) were randomly assigned to two treatment groups (15 patients in the FMS group and 17 in the FES group). Stimulation was applied continuously at 10 Hz in both groups. For FMS, the magnetic stimulator unit was set on an armchair type seat and had a concave-shaped coil, so that the patients could sit during stimulation. For FES, a vaginal electrode was used in the women and a surface electrode on the dorsal part of the penis was used in the men. Cystometry was performed before and during the stimulation. RESULTS: The bladder capacity at the first desire to void and the maximum cystometric capacity increased significantly during stimulation compared with prestimulation levels in both groups (P = 0.0054 and 0.0026, respectively, in the FMS group and P = 0.0015 and 0.0229, respectively, in the FES group). However, the increase in the maximum cystometric capacity was significantly (P = 0.0135) greater in the FMS group (114.2 +/- 124.1 mL or an increase of 105. 5% +/- 130.4% compared with the pretreatment level) than that in the FES group (32.3 +/- 56.6 mL or an increase of 16.3% +/- 33.9%). Detrusor overactivity was abolished in 3 patients in the FMS group but not in any patient in the FES group. CONCLUSIONS: Although both treatments were effective, the inhibition of detrusor overactivity appeared greater in the FMS group than in the FES group.

Adult↗
PubMed2000

Micturitional disturbance in neuro-Behçet's syndrome.

BACKGROUND: Micturitional disturbance is known to occur in neuro-Behçet's syndrome (NBS). However, its pathophysiology is uncertain and few data are available concerning urodynamic findings. We describe our findings on micturitional histories and urodynamic studies in patients with NBS. METHODS: A history of urinary symptoms was obtained from nine patients with NBS [seven male, two female, aged 26 to 54 years; mean, 41 years]. Neurological and CT/MRI findings indicated that their lesions were located mainly in the cerebral cortex, basal ganglia, cerebellum, brainstem and the spinal cord. Symptomatic patients underwent urodynamic studies, including measurement of post-micturition residuals, urethral pressure profilometry and EMG cystometry. RESULTS: Six of the nine patients (67%) had urinary symptoms that included diurnal urinary frequency in five, sensation of urgency in five, urge urinary incontinence in five, voiding difficulty in five and nocturnal urinary frequency in four. None had urinary retention. Urodynamic studies performed in six patients showed post-micturition residuals in five (50-180 ml), increased maximum urethral closure pressure in two, decrease in four and increase in one of bladder capacities, detrusor hyperreflexia in five, decreased bladder sensation in one, brisk bulbocavernosus reflex in four, detrusor-sphincter dyssynergia in two and neurogenic sphincter EMG in one. CONCLUSION: Our results indicate that micturitional disturbance is not rare in patients with NBS. Supranuclear pelvic nerve dysfunction seems to be mainly responsible for the disturbance.

Adult↗
PubMed2000

Pressure-flow study as an evaluating method of neurogenic urethral relaxation failure.

Voiding difficulty is a common feature in neurological diseases, which can be attributed to dysfunction of the urethral sphincter and the detrusor. Electromyography (EMG)-cystometry can reveal the presence of detrusor-external sphincter dyssynergia (DESD), however, internal sphincter function on voiding is not easily evaluated. Pressure-flow study is widely used to diagnose benign outlet obstruction due to prostatic hypertrophy. We applied pressure-flow study in neurological patients in order to evaluate neurogenic urethral relaxation failure. We recruited 71 patients with neurological diseases. All were men under 60 years, with mean age of 44 years, ranging from 18 to 59 years. None had abnormal finding of digital examination or ultrasound echography of the prostate. Standard cystometry showed detrusor hyperreflexia in 33 patients and residual urine was noted in 36. DESD was noted in seven of 43 patients. Pressure-flow relation curve and a detrusor pressure (P(det)) at the point of maximum flow rate (Q(max)) (i.e., P(det)Q(max)) were obtained by urodynamic computers. The Abram-Griffiths (AG) number (P(det)Q(max)-2Q(max)), showing outlet obstruction particularly over 40, was also obtained. The points of P(det)Q(max) of the patients fell into three categories of the AG nomogram, showing obstruction in 19.7%, equivocal in 52.1% and unobstructed in 28.2%. Patients with DESD had AG number over 40 more commonly (57.1%) than those without DESD (8.4%) (p<0.05). The mean AG number was 46.4 in patients with DESD, which was larger than 17.1 in patients without DESD (p<0.01). Patients with detrusor hyperreflexia had AG number over 40 more commonly (42.4%) than those with normal cystometric curve (0%) (p<0.01). The mean AG number was 30.6 in patients with detrusor hyperreflexia, which was larger than 13.6 in patients with normal cystometric curve (p<0.01). The results showed that 19.7% of patients with neurological diseases had obstructive pattern (high pressure voiding), evidence of urethral relaxation failure with relatively preserved detrusor contraction. DESD is a factor contributing to the urethral relaxation failure of the patients. The results also indicated a relationship between detrusor hyperreflexia and obstructed pattern, probably reflecting co-occurrence of detrusor hyperreflexia with DESD or detrusor-internal sphincter dyssynergia.

Adolescent↗
PubMed2000

Are alpha-blockers involved in lower urinary tract dysfunction in multiple system atrophy? A comparison of prazosin and moxisylyte.

Lower urinary tract dysfunction is a major cause of morbidity in patients with multiple system atrophy (MSA). alpha1-Adrenergic receptors are present in the proximal urethra where impaired relaxation may be responsible for voiding difficulty and a large amount of residual urine. An open study was designed to evaluate whether the blockade of these receptors by prazosin (a nonselective alpha1 blocker) and moxisylyte (an alpha1A-selective blocker) would improve bladder emptying in patients with MSA. Post-micturition residual volumes and clinical symptoms of 49 patients with MSA were evaluated at trial entry and after 4 weeks (prazosin; n=21 and moxisylyte; n=28). The respective means for the prazosin and moxisylyte groups were 38.1% and 35.2% reductions in residual urine volume (P<0.05), and there was lessening of urinary symptoms. Side effects due to orthostatic hypotension were seen in 23.8% of the prazosin group but in only 10.7% of the moxisylyte group. These effects were common in patients with postural hypotension of more than -30 mmHg at trial entry (P<0.05). Modulation of alpha1-receptors may function in the management of lower urinary tract dysfunction in MSA.

Adrenergic alpha-Antagonists↗
PubMed2000

Identification of the promoter region of human placental 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene.

The placenta-type isozyme of human 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (HP2K) is expressed in several tissues such as placenta, brain, testis, liver, kidney, skeletal muscle, and primary blood mononuclear cells. To better understand the regulation of HP2K gene expression, we isolated and characterized its genomic DNA, which includes the promoter region. The results of oligo-capping analysis indicate that the transcription start point (tsp) is an adenine residue 329 bp upstream of the translational start codon. DNA sequence analysis of this gene shows that the promoter region that contains the TATA box sequence and the 5'-UTR is different from the other known PFK-2/F2, 6BPase genes. In addition, its 5'-flanking and 5'-UTR both have G + C-rich sequences containing Sp1 binding sites. To identify the promoter/enhancer region of HP2K gene, we performed transfection analyses of human choriocarcinoma BeWo cells with HP2K promoter-luciferase constructs. These experiments identified a promoter region 164 bp upstream from the tsp and an enhancer region between -1265 and -1329 on the 5'-flanking sequences. We also showed that Sp1 sites were not essential for HP2K transcription. Following transfection, stimulation experiments with serum, progesterone and phorbol 12-myristate 13-acetate showed that only the construct with the enhancer containing putative early growth response-1 binding motif was responsive to serum. We propose that the transcription of HP2K is strictly controlled by tissue-specific factors even though its genomic DNA contains several transcriptional elements.

5' Untranslated Regions↗