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Biomedical subjects

K Ishizu

Publications and source records attributed to K Ishizu.

At least 19 recordsLinked to original sources

Solution Properties of Star-Shaped Polystyrenes Having Peripheral Charged Ions.

Functionalized polystyrene stars were prepared by copolymerization of polystyryl lithium with divinylbenzene in a mixture of benzene/tetrahydropyran, where the polystyrene arms were prepared by anionic polymerization using [2-[(N,N-dimethylamino)-methyl]phenyl]lithium as the initiator. These functional stars were converted by quaternization with methyl iodide into polystyrene stars having peripheral positive charges. We studied the charge effects on the solution properties of such stars. The hydrodynamic dimension of peripheral charged polystyrene (PS) stars depended strongly on the solubility parameter between PS segments and solvent. Copyright 2000 Academic Press.

Journal Article↗

Positron emission tomography of radioligand binding in porcine striatum in vivo: haloperidol inhibition linked to endogenous ligand release.

The ligands N-methylspiperone and haloperidol both bind to D(2)-like dopamine receptors. The competitive nature of the binding over a wide range of haloperidol concentrations and the effect on dopamine release have never been tested in vivo. We determined the competitive interaction between 3-N-[(11)C]methylspiperone ([(11)C]NMSP) and haloperidol binding to striatal dopamine D(2)-like receptors with positron emission tomography (PET) of pig brain. [(11)C]NMSP tomography was performed with haloperidol at five different plasma concentrations maintained constant by programmed infusion. Kinetic parameters of ligand competition for binding in the striatum were determined by deconvolving time-activity curves of the striatum and cerebellum from metabolite-corrected arterial plasma [(11)C]NMSP and haloperidol concentrations. Two types of [(11)C]NMSP-binding sites were evident in the striatum, both saturable by haloperidol administration. The preponderant or primary sites bound [(11)C]NMSP irreversibly, as dopamine D2-like receptors, while the secondary sites bound [(11)C]NMSP reversibly, as do serotonin S2 receptors. Woolf-Hanes plots revealed the predicted approximately linear relationships between the binding indices and the haloperidol plasma concentration. For the irreversible binding sites, this relationship indicated a 50% inhibitory concentration of haloperidol of 2 nM in plasma and a maximum binding capacity of 64 pmol cm(-3) in striatum. For the reversible binding sites, the relationship indicated a 50% inhibitory plasma concentration of haloperidol of 1 nM and a maximum binding capacity of 4.5 pmol cm(-3). Second-order polynomial Eadie-Hofstee-Scatchard plots were consistent with increased competition from an endogenous ligand of the irreversibly binding sites only with increasing doses of haloperidol. At the highest haloperidol dose, this hypothetical endogenous ligand had risen 6-7-fold. We contend that this reveals the release of dopamine by high concentrations of haloperidol.

Animals↗

Increased cortical activation during hearing of speech in cochlear implant users.

To investigate the cortical activities while listening to noise and speech in cochlear implant (CI) users, we compared cerebral blood flow in postlingually deafened CI users with that in normal hearing subjects using positron emission tomography. While noise activation in CI users did not significantly differ from that in normal subjects, hearing speech activated more cortical areas in CI users than in normal subjects. A comparison of speech activation in these two groups revealed higher activation in CI users not only in the temporal cortices but also in Broca's area and its right hemisphere homologue, the supplementary motor area and the anterior cingulate gyrus. In postlingually deafened subjects, the hearing of speech coded by CI may be accompanied by increased activation of both the temporal and frontal cortices.

Adult↗

Detection and a possible mechanism of magnetic field effect on the crystal growth of sedimentary calcium carbonate.

Sedimentary calcium carbonate was grown at a physiological pH6.8 from a mixture of equivolume of 70 mM Ca(NO(3))(2) and 70 mM NaHCO(3) aqueous solution. The kinetics of the crystal growth was monitored by means of turbidity measurement. The apparent absorption is gradually increased with the elapsed time after the mixing and reaches its maximum at t(max). The average t(max) is significantly decreased from =467 s (for n=13 runs) to 408 s (n=13) by application of the static magnetic field (SMF) of H=400 mT to the precipitating solution. The application of SMF at 120 s later the mixing shows the same =396 s (n=9) as that of 408 s. It has been thus detected that the application of SMF is ineffective in the stage of the nucleation or the earlier stage of the crystal growth but effective in the Ostwald ripening stage of the growth nucleus or the later stage of the crystal growth where large numbers of the growing crystalline particles seem greater than a few hundred nanometers. A possible mechanism for the SMF effect is as follows. An ion escaping from the growing crystal surface with a certain 'migration velocity' due to a random walk process has significant probability to drift onto the identical surface or at least the identical crystal by means of Lorentz force, because the translational displacement of the crystal during a cycle of the cyclotron motion of the ion is smaller than the size of the growing crystal. This type of drift results in the suppression of re-dissolution of the ions on the growing surface and in the acceleration of the growth in the later stage of the crystal growth. The undetected SMF effect in the earlier stage of the crystal growth can be partly attributed to the re-dissolution due to the thermodynamic instability of the small nuclei which predominates over the presumable SMF effect. This can be partly ascribed to the large translational displacement of the small particle. The application of this mechanism to an oscillating magnetic field will predict the presence of a window for the frequency of the oscillating magnetic field.

Journal Article↗

The magnetic field effect affecting on the metallic chemical components of egg shell as demonstrated for breeding chicken.

The chickens were raised under fixation of the permanent magnet (80 mT) and the effect of extra magnetic field, which affects on the content of the several inorganic chemical elements of egg shell, was investigated by X-ray fluorescence spectroscopy. From 3 days after fixing the magnet, the relative concentration of Ca begun to increase. After 10 days, the relative contents of Ca were decreased, while conversely the contents of K were increased. Though there was a linear relationship between Ca content and P content in inner layer of chicken egg shell, the relationship was greatly hindered by applying the static magnetic field. The experimental result suggests that both Ca and K ion transport can be perturbed by addition of extra magnetic field in the incubation processes of chicken egg, and that Ca, P and K ions play the important role in egg shell formation.

Journal Article↗

Cortical networks subserving the perception of tinnitus--a PET study.

Subjective tinnitus is an auditory phantom perception that may arise from any aberrant signal within the auditory system. Further processing of this signal and the conscious perception of tinnitus takes place in the cerebral cortex. A few functional brain-imaging studies have been performed to elucidate the underlying cerebral mechanisms of this perception. These studies mostly concern rare types of tinnitus (e.g. tinnitus changeable by oral-facial movements), or compared tinnitus patients with healthy volunteers. These studies attributed variable activation of the primary auditory cortices, associative auditory cortices and the left hippocampus to the perception of tinnitus. Based on these heterogeneous results, no consensus on the underlying mechanisms has been reached. The aim of the present study was to obtain further details of the central perception and processing of the tinnitus signal. Positron emission tomography (PET) was used to map the tinnitus-specific central activity. By contrasting PET-images of suppressed tinnitus with PET-images of the habitual tinnitus sensation, we were able to identify a right prefrontal-temporal network associated with the perception of tinnitus. Besides the evidence of activation of associative auditory sensory regions, the results indicated that activation of cortical centres subserving attention and emotion may underlie the continuous irritability associated with severe tinnitus.

Adult↗

Potent antitumor activity of MS-247, a novel DNA minor groove binder, evaluated by an in vitro and in vivo human cancer cell line panel.

We synthesized a novel anticancer agent MS-247 (2-[[N-[1-methyl-2-[5-[N-[4-[N,N-bis(2-chloroethyl) amino] phenyl]] carbamoyl]-1H-benzimidazol-2-yl] pyrrol-4-yl] carbamoyl] ethyldimethylsulfonium di-p-toluenesulfonate) that has a netropsin-like moiety and an alkylating residue in the structure. We evaluated antitumor activity of MS-247 using a human cancer cell line panel coupled with a drug sensitivity database and subsequently using human cancer xenografts. The average MS-247 concentration required for 50% growth inhibition against a panel of 39 cell lines was 0.71 microM. The COMPARE analysis revealed that the differential growth inhibition pattern of MS-247 significantly correlated with those of camptothecin analogues and anthracyclins, indicating that MS-247 and the two drug groups might have similar modes of action. MS-247 exhibited remarkable antitumor activity against various xenografts. A single i.v. injection of MS-247 significantly inhibited the growth of all 17 xenografts tested, which included lung, colon, stomach, breast, and ovarian cancers. In many cases, MS-247 was more efficacious than cisplatin, Adriamycin, 5-fluorouracil, cyclophosphamide, VP-16, and vincristine and was almost comparable with paclitaxel and CPT-11; these are the most clinically promising drugs at present. MS-247 was noticeably more effective than paclitaxel (in HCT-15) and CPT-11 (in A549, HBC-4, and SK-OV-3). The toxicity of MS-247, indicated by body weight loss, was reversible within 10 days after administration. The MS-247 mode of action showed DNA binding activity at the site where Hoechst 33342 bound, inhibited topoisomerases I and II (as expected by the COMPARE analysis) blocked the cell cycle at the G2-M phase, and induced apoptosis. These results indicate that MS-247 is a promising new anticancer drug candidate to be developed further toward clinical trials.

Animals↗

Synthesis and Structural Ordering of Gradient-Modulus Star Copolymers.

Gradient-modulus star copolymers were synthesized by crosslinking of polystyrene/isoprene tapered anions with divinylbenzene in benzene. The styrene content in the tapered arm was determined by 1H-nuclear magnetic resonance as a parameter of conversion. The composition of the arm showed the gradient structure and was in good agreement with that calculated by reactivity ratios. The solution properties of gradient-modulus star copolymers were examined by static and dynamic light scatterings. The structural ordering of gradient-modulus star copolymers were investigated by means of small-angle X-ray scattering. Gradient-modulus star copolymers formed a body-centered cubic (BCC) structure near the overlap threshold (C*). Above C*, this structure changed to the mixed lattice of BCC and face-centered cubic (FCC) structures. Copyright 1999 Academic Press.

Journal Article↗

Positron emission tomography of cortical centers of tinnitus.

Tinnitus is associated with a wide variety of disorders in the auditory system. Whether generated peripherally or centrally, tinnitus is believed to be associated with activity in specific cortical regions. The present study tested the hypothesis that these cortical centers subserve the generation, perception and processing of the tinnitus stimulus and that these processes are suppressed by lidocaine and masking. Positron emission tomography was used to map the tinnitus-specific central activity. By subtracting positron emission tomography images of regional cerebral blood flow distribution obtained during suppression of the tinnitus from positron emission tomography images obtained during the habitual tinnitus sensation, we were able to identify brain areas concerned with the cerebral representation of tinnitus. Increased neuronal activity caused by tinnitus occurred predominantly in the right hemisphere with significant foci in the middle frontal and middle temporal gyri, in addition to lateral and mesial posterior sites. The results are consistent with the hypothesis that the sensation of tinnitus is associated with activity in cortical regions functionally linked to subserve attention, emotion and memory. For the first time, the functional anatomy of conditions with and without the habitual tinnitus sensation was obtained and compared in the same subjects.

Adult↗

Stimulus-dependent central processing of auditory stimuli: a PET study.

Positron emission tomography (PET) was used to investigate the neural systems involved in the central processing of different auditory stimuli. Noise, pure tone and pure-tone pulses, music and speech were presented monaurally. O-15-water PET scans were obtained in relation to these stimulations presented to five normal hearing and healthy subjects. All stimuli were related to a basic scan in silence. Processing of simple auditory stimuli, such as pure tones and noise, predominantly activate the left transverse temporal gyrus (Brodmann area [BA] 41), whereas sounds with discontinued acoustic patterns, such as pure-tone pulse trains, activated parts of the auditory association area in the superior temporal gyri (BA 42) in both hemispheres. Moreover, sounds with complex spectral, intensity, and temporal structures (words, speech, music) activated spatially even more extensive associative auditory areas in both hemispheres (BA 21, 22). PET has revealed a remarkable potential to investigate early central auditory processing, and has provided evidence of the coexistence of functionally linked, but individually active parallel and serial auditory networks.

Acoustic Impedance Tests↗

Nuclear transport of the major capsid protein is essential for adeno-associated virus capsid formation.

Adeno-associated virus capsids are composed of three proteins, VP1, VP2, and VP3. Although VP1 is necessary for viral infection, it is not essential for capsid formation. The other capsid proteins, VP2 and VP3, are sufficient for capsid formation, but the functional roles of each protein are still not well understood. By analyzing a series of deletion mutants of VP2, we identified a region necessary for nuclear transfer of VP2 and found that the efficiency of nuclear localization of the capsid proteins and the efficiency of virus-like particle (VLP) formation correlated well. To confirm the importance of the nuclear localization of the capsid proteins, we fused the nuclear localization signal of simian virus 40 large T antigen to VP3 protein. We show that this fusion protein could form VLP, indicating that the VP2-specific region located on the N-terminal side of the protein is not structurally required. This finding suggests that VP3 has sufficient information for VLP formation and that VP2 is necessary only for nuclear transfer of the capsid proteins.

Amino Acid Sequence↗

Idiopathic clitoral hypertrophy.

We report a case of clitoral hypertrophy of unknown origin. A 3-year-old girl showed clitoral hypertrophy at birth. Biochemical analysis of peripheral blood and endocrinological examinations were normal. Other virilizing symptoms were not recognized. Clitoroplasty was carried out, and the clitoris has not enlarged 20 months after the operation. Her mother was administered cefotiam and terbutaline (beta-stimulant) during pregnancy because of threatened abortion. No virilizing agents such as progesterone were used during pregnancy.

Abortion, Threatened↗

[A case of multiloculated retroperitoneal abscess successfully treated by percutaneous drainage with a Malecot catheter].

Percutaneous catheter drainage offers an attractive alternative to open surgical drainage as the first choice in the treatment of retroperitoneal abscess. However, multiloculated abscess is difficult to drain percutaneously. We report a case of multiloculated retroperitoneal abscess successfully treated by percutaneous drainage with a Malecot catheter. A 47-year-old woman complained of fever and left flank pain. The peripheral while blood cell count was 16,800/mm3 and the blood sugar was 369 mg/dl. The computer tomographic (CT) scan showed a large multiloculated mass in the left retroperitoneum. An aspiration needle was inserted into the perinephric mass under ultrasonographic guidance. The definitive diagnosis of abscess was made by aspiration of purulent fluid. A 20 Fr. Malecot catheter was passed over the guide wire under fluoroscopic guidance. Two hundred ml of pus was smoothly aspirated. Streptococcus agalactiae was isolated from the aspirate. Antibiotics and insulin were started. The catheter was retained for 49 days until ultrasonography revealed disappearance of the abscess. One year later, she had no symptoms of recurrence.

Abdominal Abscess↗

[Two cases of testicular infarction: the usefulness of enhanced MRI for preoperative diagnosis].

The differential diagnosis in acute scrotum, particularly torsion of spermatic cord and epididymitis, is sometimes difficult. An erroneous diagnosis may result in unnecessary and improper treatment. We report two cases of testicular infarction including torsion of spermatic cord, preoperatively diagnosed by enhanced magnetic resonance imaging (MRI). Case 1: A 16-year-old boy presented with a 3-day history of left scrotal swelling and left lower abdominal pain. He had fever and leukocytosis. Antibiotics for 2 days failed to relieve the symptoms. Enhanced MRI showed absence of blood flow in the left testis. Scrotal exploration revealed hemorrhage and necrosis in the left testis. Left orchiectomy and right orchiopexy were performed. Case 2: A 12-year-old boy visited with scrotal swelling and fever 30 hours after an acute onset of left scrotal pain. Enhanced MRI showed absence of blood flow in the left testis. Exploration revealed left necrotic testis with torsion of spermatic cord. Left orchiectomy and right orchiopexy were performed. Our two cases suggested that enhanced MRI, by which the intratesticular blood flow can be evaluated, may be useful for the diagnosis of testicular infarction.

Adolescent↗

[A case of multiple endocrine neoplasia type 2A (MEN2A) with a mutation in the RET gene].

A 44-year-old woman complained of headache and palpitation. Magnetic resonance imaging showed bilateral adrenal tumors 10 x 9 cm in size on the left side and 8 x 4 cm in size on the right side. CT scan revealed a 0.7 x 0.7 cm mass in the thyroid. Hormonal examinations showed high values of urinary cathecholamines and serum calcitonin. DNA sequence analysis of peripheral white blood cells revealed that codon 634 in exon 11 of the RET gene was mutated from TGC (Cys) to TAC (Tyr). From these findings, a diagnosis was made of MEN2A with bilateral adrenal pheochromocytomas and medullary thyroid carcinoma. Bilateral adrenalectomy and thyroidectomy were performed. The same mutation of the RET gene was detected in all her 3 children, in two of whom, early stage medullary thyroid carcinoma was detected and thyroidectomy was performed. DNA analysis of the RET gene was useful for the diagnosis of carriers of MEN2A and the early detection of medullary thyroid carcinoma.

Adolescent↗

[Combined treatment with CDDP and radiation effective against neuroendocrine carcinoma of the urinary bladder: a case report].

A case of neuroendocrine carcinoma (small cell carcinoma) of the urinary bladder is presented. A 76-year-old man complaining of dysuria visited our clinic on October 31, 1997. On physical examination, a huge mass was palpable in the lower abdomen. Abdominal and pelvic computed tomographic (CT) scan revealed a huge mass, 6.7 x 6.0 cm in size, with extravesical extension in the anterior wall of the urinary bladder and no metastatic lesions. Percutaneous biopsy of the tumor revealed undifferentiated neuroendocrine carcinoma. The value of serum neuron specific enolase (NSE) was 220 ng/ml (normal range: 0-10 ng/ml). Twenty days after the first CT scan, the tumor had grown to be 12.5 x 11.0 cm in size. He was treated with combination therapy of systemic cisplatin and external pelvic radiation and then achieved complete remission on CT scan and biopsy. The value of serum NSE was normalized. Four months later, abdominal CT scan revealed a huge metastastic lesion in the paraaortic and parahepatic regions, but, no local recurrence in the bladder. The value of serum NSE was 240 ng/ml. He was treated with 4 cycles of systemic combination therapy of cisplatin and etoposide. He achieved partial remission (regression rate: 77%) on CT scan after completion of the first 2 cycles, but the tumor showed rapid re-growth and he died of cancer 1 month later despite another 2 cycles. These combination therapies were effective against neuroendocrine carcinoma of the urinary bladder, although, the duration of the effect was short.

Aged↗

Quantitative PET analysis of regional cerebral blood flow and glucose and oxygen metabolism in response to fenfluramine in living porcine brain.

The serotonin agonist fenfluramine has been used widely in humans for studying neuronal activation. We carried out the present study in order to determine whether anesthetized pigs could be used for studying effects of fenfluramine on cerebral functions using positron emission tomography (PET). We obtained quantitative measures of regional cerebral blood flow (rCBF) and of glucose and oxygen utilization (rCMRglc and rCMR(O2)) during intravenous administration of fenfluramine, using [15O]water, [18F]FDG and [15O]oxygen, respectively. Fenfluramine (25 mg/h i.v.) caused a significant rise in rCBF and, to a lesser extent, in rCMR2(O2), but it failed to affect rCMRglc. The findings indicate that quantitative estimation of rCBF by repeated injection of [15O]water was more sensitive than either rCMRO2 or rCMRglc for detecting effects of fenfluramine on serotonin neurotransmission in living porcine brain.

Animals↗