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Biomedical subjects

Takashi Tominaga

Publications and source records attributed to Takashi Tominaga.

14 recordsLinked to original sources
PubMed2006

Clinical efficacy of an alpha1A/D-adrenoceptor blocker (naftopidil) on overactive bladder symptoms in patients with benign prostatic hyperplasia.

AIM: We evaluated the efficacy of an alpha1a/d blocker, naftopidil, on storage symptoms in patients with benign prostatic hyperplasia (BPH), using frequency/volume charts (FVC). METHODS: A total of 81 patients with BPH (52-91 years, mean age 69.0 years) were studied. The inclusion criteria were: (i) one or more episode(s) of urinary urgency/day; (ii) a score of eight or more points on the International Prostate Symptom Score (I-PSS); and (iii) three or more points in any of the scores for three items (frequency, nocturia, and urgency) of the I-PSS. The patients received 50-75 mg/day of naftopidil for 6 weeks. All the patients were examined for 2-day FVC before and after the administration of naftopidil. I-PSS, quality of life index, and uroflowmetry were also evaluated. RESULTS: Total I-PSS decreased from 19.1 to 10.5 points (P < 0.0001), with significant improvement of both storage and voiding symptom scores (P < 0.0001, both). The score for urgency decreased from 3.1 to 1.4 (P < 0.0001). Daytime and night-time frequency decreased from 9.3 to 8.0 (P < 0.0001) and from 2.7 to 2.0 (P = 0.0009), respectively. Mean volume/void increased from 174.0 to 188.6 mL (P = 0.0453). Nocturia decreased from 3.2 to 2.3 (P < 0.0001) in 40 patients who suffered from nocturia two times or more. Notably, significant improvement of nocturia was observed in the patients both with and without nocturnal polyuria (P = 0.0006 and 0.0135, respectively). CONCLUSION: The alpha1a/d blocker naftopidil improves not only voiding symptoms but also storage symptoms, and is effective for nocturia in patients with BPH regardless of the existence of nocturnal polyuria.

Adrenergic alpha-Antagonists↗
PubMed2006

[Age specific reference ranges and clinical trial for complexed prostate specific antigen (cPSA)].

We compared the complexed PSA (cPSA) reference range of values by age against that for total PSA. The subjects were 1,210 men who underwent a complete medical checkup at our center between September and November 2003. We found an upward trend of the measured values associated with age and defined a set of expected result range by age groups. The cPSA 95th percentile upper limit value increased across all age groups: for men under 40 years, 1.38ng/ml: for men 40 to 49 years, 1.60ng/ml; for men 50 to 59 years, 2.25 ng/ml; for men 60 to 69 years, 2.50 ng/ml; and for men 70 years older, 4.31 ng/ml (The number of subjects in each group was 153, 323, 429, 220 and 77). The total PSA also increased with age: 1.85 ng/ml, 2.11 ng/ml, 2.80 ng/ml, 4.20 ng/ml, and 5.69 ng/ml, respectively. We also compared other prostatic tumor markers in urology patients.

Adult↗
PubMed2005

Cholinergic modulation of the spatiotemporal pattern of hippocampal activity in vitro.

The aim of this study was to use optical imaging with voltage-sensitive dyes (Di-4-ANEPPS), to examine the cholinergic modulation of CA1 network responses to Schaffer collateral input. By comparing responses recorded with optical imaging and field recordings across the proximodistal axis of CA1, it was initially demonstrated that voltage-sensitive dyes could report reliably both the pattern of activation and cholinergic modulation. The higher spatial resolution of optical imaging was used to explore the somatodendritic profile of cholinergic modulation. It was found that activation of muscarinic acetylcholine receptors (mAChR) (1-10 microM carbachol), inhibited evoked responses across all layers of CA1. This was accompanied by an increase in paired-pulse facilitation in the apical and distal dendritic layers (40 ms inter-stimulus interval), but not in perisomatic regions. The mAChR antagonist, 20 microM atropine, alone increased facilitation at perisomatic sites, suggesting that muscarinic signalling pathways actively suppress perisomatic responses to repetitive stimulation. In contrast, the activation of nicotinic acetylcholine receptors (10 microM nicotine) had no significant effect on single evoked responses, but selectively increased facilitation at perisomatic sites. These results suggest that cholinergic modulation of the hippocampal CA1 network has multiple differential effects on the somatodendritic processing of the Schaffer collateral input.

Acetylcholine↗
PubMed2005

Electrical properties and fusion dynamics of in vitro membrane vesicles derived from separate parts of the contractile vacuole complex of Paramecium multimicronucleatum.

The contractile vacuole complex of Paramecium multimicronucleatum transforms into membrane-bound vesicles on excision from the cell. The I-V relationship was linear in a voltage range of -80 to +80 mV in all vesicles, despite being derived from different parts of the contractile vacuole complex. No voltage-gated unit currents were observed in membrane patches from the vesicles. Vesicles derived from the radial arm showed a membrane potential of >10 mV, positive with reference to the cytosol, while those derived from the contractile vacuole showed a residual (<5 mV) membrane potential. The electrogenic V-ATPases in the decorated spongiome are responsible for the positive potential, and Cl- leakage channels are responsible for the residual potential. The specific resistance of the vesicle membrane (approximately 6 kOmega cm2) increased, while the membrane potential shifted in a negative direction when the vesicle rounded. An increase in the membrane tension (to approximately 5 x 10(-3) N m(-1)) is assumed to reduce the Cl- leakage conductance. It is concluded that neither voltage- nor mechano-sensitive ion channels are involved in the control of the fluid segregation and membrane dynamics that govern fluid discharge cycles in the contractile vacuole complex. The membrane vesicles shrank when the external osmolarity was increased, and swelled when the osmolarity was decreased, implying that the contractile vacuole complex membrane is water permeable. The water permeability of the membrane was 4-20 x 10(-7) microm s(-1) Pa(-1). The vesicles containing radial arm membrane swelled after initially shrinking when exposed to higher external osmolarity, implying that the V-ATPases energize osmolyte transport mechanisms that remain functional in the vesicle membrane. The vesicles showed an abrupt (<30 ms), slight, slackening after rounding to the maximum extent. Similar slackening was also observed in the contractile vacuoles in situ before the opening of the contractile vacuole pore. A slight membrane slackening seems to be an indispensable requirement for the contractile vacuole membrane to fuse with the plasma membrane at the pore. The contractile vacuole complex-derived membrane vesicle is a useful tool for understanding not only the biological significance of the contractile vacuole complex but also the molecular mechanisms of V-ATPase activity.

Animals↗
PubMed2005

[Two cases of hemodialysis patients with absolute hypoparathyroidism or normal parathyroid function who were suffering from prostate carcinoma].

In recent years, the incidence of prostate carcinoma in patients with renal failure is increasing. But it is difficult to diagnose the occurrence of this neoplasm because of decrease of urinary volume in these patients. Two hemodialysis patients (age: 64, 68 years, the duration of hemodialysis: 10, 8 years) suffering from prostate carcinoma were treated with androgen deprivation therapy, which accelerates bone resorption. (This kind of osteoporosis is often treated by bisphosphonate, but this treatment is prohibited in hemodialysis patients.) Both serum testosterone and estradiol went down to the extremely lower levels in these patients. Thereafter, one (case 2) of them was maintained under absolute hypoparathyroidism by the conservative therapy with vitamin D. As a result, bone mineral density of the patient (case 2) was well maintained during one year. In conclusion, hypoparathyroidism was helpful to prevent bone loss in patients receiving androgen deprivation therapy.

Aged↗
PubMed2004

Expanded dynamic range of fluorescent indicators for Ca(2+) by circularly permuted yellow fluorescent proteins.

Fluorescence resonance energy transfer (FRET) technology has been used to develop genetically encoded fluorescent indicators for various cellular functions. Although most indicators have cyan- and yellow-emitting fluorescent proteins (CFP and YFP) as FRET donor and acceptor, their poor dynamic range often prevents detection of subtle but significant signals. Here, we optimized the relative orientation of the two chromophores in the Ca(2+) indicator, yellow cameleon (YC), by fusing YFP at different angles. We generated circularly permuted YFPs (cpYFPs) that showed efficient maturation and acid stability. One of the cpYFPs incorporated in YC absorbs a great amount of excited energy from CFP in its Ca(2+)-saturated form, thereby increasing the Ca(2+)-dependent change in the ratio of YFP/CFP by nearly 600%. Both in cultured cells and in the nervous system of transgenic mice, the new YC enables visualization of subcellular Ca(2+) dynamics with better spatial and temporal resolution than before. Our study provides an important guide for the development and improvement of indicators using GFP-based FRET.

Animals↗
PubMed2004

Detection of the archetypal regulatory region of JC virus from the tonsil tissue of patients with tonsillitis and tonsilar hypertrophy.

The regulatory regions of JC virus (JCV) DNAs in the brain of patients with progressive multifocal leukoencephalopathy (PML) (designated as PML-type regulatory regions) are hypervariable, whereas those in the urine and renal tissue of individuals without PML have the same basic structure, designated as the archetype. It is thought that JCV strains with the archetypal regulatory region circulate in the human population. Nevertheless, Monaco et al (J Virol 70: 7004-7012, 1996) reported that PML-type regulatory regions occur in human tonsil tissue. The purpose of this study is to confirm their findings. Using nested polymerase chain reaction (PCR), the authors detected the regulatory region of JCV DNA in the tonsil tissue from 14 (44%) of 32 donors with tonsillitis and tonsilar hypertrophy. Sequencing of the detected regulatory regions indicated that they were identical with the archetypal regulatory regions detected previously or, in a few cases, slightly deviated from the archetype. This finding suggests not only that tonsil tissue is the potential site of initial JCV infection but also that archetypal JCV strains circulate in the human population.

Adult↗
PubMed2002

Identification of multiple novel epididymis-specific beta-defensin isoforms in humans and mice.

Defensins comprise a family of cationic antimicrobial peptides that are characterized by the presence of six conserved cysteine residues. We identified two novel human beta-defensin (hBD) isoforms by mining the public human genomic sequences. The predicted peptides conserve the six-cysteine motif identical with hBD-4, termed hBD-5 and hBD-6. We also evaluated the characteristics of the mouse homologs of hBD-5, hBD-6, and HE2beta1, termed mouse beta-defensin (mBD)-12, mBD-11, and mouse EP2e (mEP2e). The mBD-12 synthetic peptide showed salt-dependent antimicrobial activity. We demonstrate the epididymis-specific expression pattern of hBD-5, hBD-6, mBD-11, mBD-12, and mEP2e. In situ hybridization revealed mBD-11, mBD-12, and mEP2e expression in the columnar epithelium of the caput epididymis, contrasting with the predominant expression of mBD-3 in the capsule or septum of the whole epididymis. In addition, the regional specificity of mBD-11, mBD-12, and mEP2e was somewhat overlapping, but not identical, in the caput epididymis, suggesting that specific regulation may work for each member of the beta-defensin family. Our findings indicated that multiple beta-defensin isoforms specifically and cooperatively contribute to the innate immunity of the urogenital system.

Amino Acid Sequence↗
PubMed2002

Neurodegeneration with tau accumulation in a transgenic mouse expressing V337M human tau.

Formation of neurofibrillary tangles (NFTs) is a common neuropathological feature found in several neurodegenerative diseases, including Alzheimer's disease. We have developed a transgenic (Tg) mouse expressing mutant human tau (V337M), derived from frontotemporal dementia parkinsonism-17. V337M Tg mice revealed tau aggregations in the hippocampus, which fulfills the histological criteria for NFTs in human neurodegenerative diseases. Concurrent with the accumulation of RNA and phosphorylated tau, neurons exhibited morphological characteristics of degenerating neurons, which include a loss of microtubules, accumulation of ribosomes, plasma and nuclear membrane ruffling, and swelling of the Golgi network. Thus, mutant tau induces neuronal degeneration associated with the accumulation of RNA and phosphorylated tau. The functional consequences of this neuronal degeneration was evidenced by the reduction of hippocampal neural activity and behavioral abnormality in Tg mice.

Amino Acid Substitution↗
PubMed2002

Development of periodic tension in the contractile vacuole complex membrane of paramecium governs its membrane dynamics.

The contractile vacuole complex is a membrane-bound osmoregulatory organelle of fresh water protozoa such as Paramecium. In Paramecium it consists of a central vacuole (the contractile vacuole) and 5-10 arms that radially extend from the vacuole into the cytosol (the radial arms). Excess cytosolic water, acquired osmotically, is segregated by the radial arms and enters the vacuole, so that the vacuole swells (the fluid-filling phase). The vacuole then rounds (the rounding phase) and the radial arms sever from the vacuole. The vacuole membrane then fuses with the plasma membrane at the pore region and the pore opens. The vacuole shrinks as its fluid is discharged through the pore (the fluid-discharging phase). The pore closes when the fluid has been discharged. The radial arms then reattach to the vacuole, so that the vacuole swells again as the fluid enters from the arms (the next fluid-filling phase). We found that the vacuole continued to show rounding and slackening even after it together with a small amount of cytosol had been isolated from the cell. Using a microcantilever placed on the surface of the vacuole the tension of the in vitro vacuole increased to 5 x 10(-3)N m(-1) as the vacuole rounds, and its lowest value was 1 x 10(-4)N m(-1) during slackening. We propose a hypothesis that an increase in the spontaneous curvature of the organelle's membrane leads to an increase in membrane tension and thus to the vacuole's rounding, severing of the radial arms from the vacuole, and opening of the pore. Conversely, a decrease in the spontaneous curvature accompanied by a decrease in membrane tension could lead to the closing of the pore and reattachment of the radial arm at the start of the fluid-filling phase.

Animals↗
PubMed2002

Optical imaging of long-lasting depolarization on burst stimulation in area CA1 of rat hippocampal slices.

Postsynaptic depolarization of dendrites paired with spike generation at the soma is considered to be a central mechanism of long-term potentiation (LTP) induction and a prime example of a Hebbian synapse. This pairing, however, has never been actually demonstrated on tetanic stimulation. Optical imaging of neural activity with a voltage-sensitive dye (VSD) is one potentially suitable method for examining this pairing. It is possible with optical recording to examine simultaneously the excitation of postsynaptic neurons at multiple sites. Thus the pairing of spike generation at the soma and dendritic depolarization can be examined with population level optical recording in highly laminar structures such as the hippocampal slice preparation. For example, one can correlate the optical signals obtained from cell layers with the activity of the soma, and, similarly, optical signals from stratum radiatum can be correlated with the activity of the apical dendrite, even though one cannot calibrate the optical signals in terms of actual membrane potential. Using the VSD aminonaphthylethenylpyridinium in rat hippocampal slices, we aimed to examine the pairing. Standard tetanic stimulation (100 Hz, 1 s) that elicited LTP in the field excitatory postsynaptic potential (fEPSP) resulted in a long-lasting depolarizing optical signal (about 2 s) that spread progressively along the known input pathway of CA1. The time course of this long-lasting depolarization was similar to that recorded intracellularly and to that reflected in the fEPSP. The long-lasting depolarization was insensitive to D,L-2-amino-5-phosphonovaleric acid (D,L-APV, 50 microM), but D,L-APV inhibited the induction of LTP; this allowed us to increase the signal-to-noise ratio of the optical signal by averaging several trials. Using this improved optical signal, we confirmed that postsynaptic cells practically "missed" spikes during tetanic stimulation in most parts of CA1, which had been suggested in the intracellular recordings. Intracellular recordings revealed a 23% reduction in input resistance, which might explain the failed spike generation at the soma via shunting. A steep spatial convergence of the depolarization along the transverse axis of area CA1 was observed. In contrast to the response resulting from a standard 100-Hz tetanus, broader activation, and paired depolarization with somatic spikes was observed on theta-burst stimulation. Overall we concluded that postsynaptic spike generation, at least in synchronous form, has less effect on LTP induction with standard tetanic stimulation, while theta-burst tetanic stimulation can elicit pairing of dendritic depolarization and somatic discharge.

Action Potentials↗
PubMed2002

[Pulmonary embolism (PE) associated with urological surgery and angiography].

As a result of the Westernization of life style in Japan, the incidence of pulmonary embolism (PE) has been increasing, mainly after surgery and vessel catheterization. We encountered 4 cases of PE associated with urological surgery and angiography during the 3 and half years since 1995; one occurred after nephrouretectomy, one after TUR-P, and two after abdominal angiography. Three patients recovered from PE, but the other is still on a respirator. As risk factors of PE, 3 patients were over 60 years old, one was obese, two had hypertension, and one had atrial fibrillation (Af). Three patients were given tranexamic acid (AMCA). Prophylactic procedures against PE, such as intermittent compression devices for the lower extremities and low-molecule heparinization, are recommended for high-risk patients. AMCA should be used with care in patients who undergo surgery and angiography.

Aged↗
PubMed2002

[A case of dural arteriovenous fistula of the inferior petrosal sinus successfully treated by transarterial and transvenous embolizations].

A 69-year-old male was admitted with chemosis and exophthalmos of his right eye. Angiograms revealed a dural arteriovenous fistula (AVF) involving the right inferior petrosal sinus. The AVF was fed by the right occipital and ascending pharyngeal arteries and drained into the cavernous sinus and right superior ophthalmic vein from the right inferior petrosal sinus. He was treated by transarterial embolization with polyvinyl alcohol in order to reduce the shunt-flow through the fistula. Then he was treated by transvenous embolization with GDC coils five days after the arterial embolization. Symptoms in his right eye have completely disappeared. Transvenous embolization combined with transarterial embolization is a useful and safe approach in the management of AVF involving the inferior petrosal sinus.

Aged↗