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Biomedical subjects

T Tahara

Publications and source records attributed to T Tahara.

At least 91 records · Page 5Linked to original sources

Progress of caloric response of vestibular neuronitis.

Progress of caloric response and subjective symptoms of 60 patients with vestibular neuronitis was evaluated by a long term follow-up study. Normalization of caloric responses was confirmed in 25 (41.7%) out of 60 patients, 20 of whom had recovered within 2 years of the onset of vertigo. The rate of the patients with canal paresis was about 90% after 1 month of the onset, and 80% after 6 months, while 50% of them still showed canal paresis after 5 or 10 years had passed. Complete relief from subjective symptoms was recognized in 34 (56.7%) cases during the follow-up period. We conclude that the prognosis of vestibular neuronitis is not always good, because vestibular function did not recover within normal levels in about half of the patients in spite of complete relief from subjective symptoms in many of them.

Adolescent↗

Vestibular neuronitis in children.

Seventeen cases of vestibular neuronitis in children, including 11 cases from the questionnaires of an epidemiological survey in Japan and 6 patients in our clinic, were examined. Sex and age distribution was 11 males and 6 females, ranging in age from 3 to 15 years. Bilateral and recurrent cases were not encountered. Fifty-three percent of children had had a preceding episode of an upper respiratory tract infection and this ratio was higher than that in adults. The etiology of vestibular neuronitis is probably many-faceted, but it is thought that upper respiratory tract infections play an important role especially in children. Vertiginous symptoms had almost subsided among children at the last visit. However, among adults, 24% of patients felt persisting unsteadiness. The disappearance of positional and positioning nystagmus was observed in 71% of children at the last visit. Caloric CP failed to recover in only 14% of all cases who were re-examined. As shown in this study, the prognosis in children is better than in adults for nystagmus and caloric response. The results of this study thus indicate that not only central compensation but also recovery of the peripheral vestibular function is more effective for bringing recovery from the vestibular disorder in children than in adults.

Adolescent↗

Detection of minimal residual disease in Philadelphia chromosome positive acute lymphoblastic leukemia: rationale for bone marrow transplantation from the polymerase chain reaction point of view.

Bone marrow transplantation (BMT) is performed as curative therapy for acute lymphoblastic leukemia (ALL). In most patients, BMT is performed at the time of remission which implies that the number of leukemic cells is less than 5% of all hematopoietic cells, namely, 0 to 10(10) leukemia cells in the body. Thus, some patients may well undergo BMT despite the fact that no leukemic cells are left in the body. In this respect, more accurate diagnosis of complete remission status would be to the patients' benefit. To detect minimal residual disease (MRD) not found by light-microscopy, further strategies are required after achieving hematological remission. Cytogenetic methods, Southern blot analysis and conventional immunological techniques can all provide accurate diagnosis, however, the sensitivity of these techniques for the detection of MRD is just as low as that of the light microscopy. Recently, polymerase chain reaction (PCR) has become available for the detection of low levels of chimeric bcr-abl transcripts in Philadelphia chromosome positive (Ph1) ALL patients. With this assay, investigators have reported MRD in patients after chemotherapy or BMT. Most patients who achieve hematological remission after conventional chemotherapy still have bcr-abl transcript detectable by PCR, confirming the general concept that this particular leukemia needs BMT in order to cure the disease. Some patients who had MRD prior to BMT continued disease free survival > 1 year after BMT with a negative PCR result and in these patients, MRD seems to have been eradicated by the BMT procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗

[Motility of isolated vestibular hair cells induced by potassium].

Many studies of the outer hair cells in cochlea have demonstrated active motility. However, very few studies have been done on vestibular hair cells. This study was designed to demonstrate the motile responses of isolated vestibular hair cells of the chick, induced by potassium promoting contraction. Reversible cell shape changes were observed in 4 of 6 type I hair cells and 3 of 5 type II hair cells by applying the contraction solution. The cell shape changes were revealed mainly in the cuticular plate and infracuticular region. It was suggested that contraction in the cuticular plate of the isolated hair cells might be converted into tension which increases the stiffness of the sensory hairs and restricts their motions, based on the results of the present study, and the structure of contractile proteins and hair behaviors reported by previous investigators.

Animals↗

[Paranasal sinusitis due to Pasteurella multocida].

A case of paranasal sinusitis due to Pasteurella multocida (P. multocida) is reported. A 39-year-old woman presented with chief complaints of rhinorrhea and headache. The patient kept a cat in her house and kept such close contact with it as to wake up by being licked every morning. Bacteriological examination revealed P. multocida isolated from her nasal discharge and also from the saliva of the cat kept by the patient. The two isolates were compatible with respect to biochemical properties, serotype and drug susceptibility. Therefore, P. multocida infection in this case was considered to have originated from the pet cat. P. multocida infection has been increasing recently. One of the reasons is a pet boom. In order to prevent acquiring the infection from a pet animal, we should have knowledge about this infection, advise the patient to avoid close contact with pets, and provide valuable information concerning these problems to society from the viewpoint of zoonosis.

Adult↗

Penetration of cefpirome into renal and prostatic tissue.

We have conducted a study on the antibacterial activity and penetration into prostatic and renal tissue of cefpirome (CPO), a new injectable cephalosporin drug, and have obtained the following results. In the target bacterium Neisseria gonorrhoeae stored in this Department (34 non-PPNG isolates, 20 PPNG isolates), the minimum inhibitory concentration (MIC) distribution of CPO was < or = 0.003-0.1 micrograms/ml for the non-PPNG isolates and 0.006-0.1 micrograms/ml for the PPNG (penicillinase-producing Neisseria gonorrhoeae) strains, with MIC90 values of 0.1 microgram/ml and 0.05 microgram/ml respectively. Concentrations in blood and in prostatic tissue were measured in 30 prostatectomy patients after intravenous injections of 1 g of CPO. The concentration in prostatic tissue reached a maximum of 52.9 micrograms/g 15 min after administration, and gradually decreased thereafter, with average values of 17.9 micrograms/g at 60 min, 10.3 micrograms/g at 180 min, 7.22 micrograms/g at 320 min (one patient) and 2.70 micrograms/g at 360 min (one patient). There was a positive correlation between prostatic tissue concentration and blood concentration at the time of tissue collection, and it is considered that CPO penetrated into the prostatic tissue to an extent dependent on its concentration in the blood. In renal tissue, measured in 4 nephrectomy patients, the CPO concentrations found were 107-148 micrograms/g in the cortex and 80.6-88.6 micrograms/g in the medulla, which were higher than the blood concentration levels in all of the subjects. These findings indicate that CPO showed sufficient concentrations in the blood and tissues for it to be considered highly useful in the treatment of urological infections.

Cephalosporins↗

Unexpected heterogeneity of PML/RAR alpha fused mRNA detected by nested polymerase chain reaction in acute promyelocytic leukemia.

We have analyzed ten APL patients using reverse transcription polymerase chain reaction (RT-PCR) technique to detect PML/RAR alpha fused mRNA. All patients in this study had PML/RAR alpha fused mRNA (three cases of the short type and seven cases of the long type), although the chromosomal translocation t(15;17) was not detected in one patient. After ethidium bromide staining, two-thirds of the short type and all cases of the long type were found to have multiple PCR products (192 and 93 base pair (bp) bands in the short type and 666, 522, 263, and 164 bp in the long type). A total of six distinct fused mRNAs were sequenced (P1R1, P1R2, P3R1, P2R1, and P2R2). Southern hybridization analysis showed only one rearranged band in each of the patients. These results suggest that the longest mRNAs in each type are the authentic fused mRNAs and the other smaller mRNAs are generated through splicing events. In RAR alpha, a novel fusion point (R2) was identified within the fourth exon. This uncommon splicing may be caused by the instability of the splicing mechanism of the rearranged PML/RAR alpha gene. Among the ten APL patients, no correlation was observed between the type of fused mRNA and the clinical characteristics examined.

Adult↗

Rat cystathionine beta-synthase. Gene organization and alternative splicing.

We elucidated the structure and alternative splicing patterns of the rat cystathionine beta-synthase gene. The gene is 20-25 kilobase pairs long, and its coding region is divided into 17 exons. These are alternatively spliced, forming four distinct mRNAs (types I through IV). The predicted open reading frames encode proteins of 61.5, 39, 60, and 52.5 kDa, respectively. Exons 13 and 16 are used alternatively and mutually exclusively. Exon 13 includes a stop codon and encodes the unique carboxyl-terminal sequence found in types II and IV. Exon 16 is present only in type I. Types I and III, which differ by 42 nucleotides (exon 16), are the predominant synthase mRNA forms in rat liver. Seventeen arginine peptides from pure liver synthase matched the deduced amino acid sequences of types I and III. These two polypeptides are detectable in liver extracts; each exhibits enzymatic activity when expressed in transfected Chinese hamster cells. Synthase shows substantial sequence similarity with pyridoxal 5'-phosphate dependent enzymes from lower organisms. Similarity of synthase to Escherichia coli O-acetylserine (thiol)-lyase (cysK) is 52%; E. coli tryptophan synthase beta chain (trpB), 36%; yeast serine deaminase, 33%. Lysine 116 in synthase aligns with the established pyridoxyllysine residue of these enzymes suggesting that it is the pyridoxal 5'-phosphate binding residue.

Amino Acid Sequence↗

Positron-emitting N-[18F]fluoroalkyl and [18F]fluoropyrrolidinyl analogues of eticlopride as potential in vivo radioligands for dopamine D2 receptors.

N-Fluoroalkyl and 4-fluoropyrrolidinyl eticlopride analogues with high affinity toward central nervous system dopamine D2 receptors in vitro were labelled with positron emitting fluorine-18 (t1/2 = 110 min), and their in vivo biodistribution was investigated in rats. N-[18F]Fluoro-ethyl and -propyl eticlopride derivatives showed poor in vivo selectivity in the rat brain. On the other hand, 4-[18F]fluoropyrrolidinyl eticlopride exhibited almost constant and relatively high striatal concentration. The striatal/cerebellar radioactivity ratio, which corresponds to the ratio of a brain D2 receptor-rich to poor region, gradually increased to 5.2-6.4, 90 min after the injection. The striatal accumulation was selectively inhibited by pre-injection of haloperidol, a dopamine D2 antagonist, without affecting accumulation in other tissues. Thus, the selective striatal accumulation of 4-[18F]fluoropyrrolidinyl eticlopride in striatal tissue appears to be due to the specific binding to dopamine D2 receptors.

Animals↗

Synthesis and pharmacology of 3,4-dihydro-3-oxo-1,4-benzoxazine-8-carboxamide derivatives, a new class of potent serotonin-3 (5-HT3) receptor antagonists.

A series of 3,4-dihydro-3-oxo-1,4-benzoxazine-8-carboxamide derivatives was synthesized and evaluated for serotonin-3 (5-HT3) receptor antagonistic activity assessed by their ability to antagonize the von Bezold-Jarish (BJ) effect in rats. Derivatives bearing 1-azabicyclo[2.2.2]oct-3-yl moiety as a basic function attached to the carboxamide at position 8 showed more potent antagonistic activity than those bearing the other three basic moieties. Structure-activity relationships of this series showed that methyl and chloro groups were more effective as substituents at positions 4 and 6, respectively. The representative compound 15 (Y-25130) in this series showed potent antagonistic activity on the BJ effect (ED50 = 1.3 micrograms/kg i.v.), high affinity for 5-HT3 receptor (Ki = 2.9 nM) and complete protection against cisplatin-induced emesis in dogs at a dose of 0.1 mg/kg i.v.

Animals↗

Purification and some properties of acidocin 8912, a novel bacteriocin produced by Lactobacillus acidophilus TK8912.

Acidocin 8912, a bacteriocin produced by Lactobacillus acidophilus TK8912, was purified by ammonium sulfate fractionation and successive chromatographies on CM-cellulose, Sephadex G-50, Sephadex G-25, and reversed-phase HPLC on Aquapore RP-300. The purified acidocin 8912 migrated as a single band on SDS-PAGE. The molecular weight was estimated to be 5200 by SDS-PAGE, and 5400 by HPLC gel filtration on TSKgel G3000PWXL. Both the amino acid composition and the N-terminal amino acid sequence analysis indicated that acidocin 8912 was a peptide composed of presumably 50 amino acids containing a Lys residue at the N-terminus. The purified acidocin 8912 showed a bactericidal effect on sensitive cells but not a bacteriolytic effect.

Amino Acid Sequence↗

Y-27152, a long-acting K+ channel opener with less tachycardia: antihypertensive effects in hypertensive rats and dogs in conscious state.

(+)-(3S,4R)-4-(N-Acetyl-N-benzyloxyamino)-6-cyano-3,4-dihydro-2,2- dimethyl- 2H-1-benzopyran-3-ol (Y-27152) is a new K+ channel opener with a long duration of action and less tachycardia. In this study, Y-27152 was compared with a K+ channel opener lemakalim and a Ca++ channel blocker nifedipine for antihypertensive activity in conscious spontaneously hypertensive rats (SHR) and two-kidney, one-clip renal hypertensive dogs (RHD). In conscious SHR, Y-27152 (0.1-1 mg/kg, p.o.) produced long-lasting dose-related decreases in systolic blood pressure. At 1 mg/kg, the maximum response occurred 5 to 7 hr after dosing, and 24 hr later, the pressure was still significantly reduced. Heart rate was not changed by these doses of Y-27152, whereas equihypotensive doses of lemakalim or nifedipine were strongly tachycardic. The cardiovascular effects of Y-27152 were antagonized by glibenclamide (20 mg/kg, i.v.). In conscious unrestrained RHD, Y-27152 at doses of 0.01, 0.03 and 0.1 mg/kg lowered blood pressure with a slow onset and long duration of action and had only a minimal effect on heart rate, whereas both lemakalim and nifedipine reduced blood pressure and markedly increased heart rate. No tolerance to the antihypertensive effect of Y-27152 (0.1 mg/kg) occurred during an 8-week repeated daily dosing to RHD and plasma renin activity, and aldosterone levels were not elevated during this period. In rat aortic rings contracted with 20 mM KCl, Y-27152 did not modify the tension; however, its desbenzyl form (Y-26763) produced vasorelaxation, and this effect was antagonized competitively by glibenclamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

The antiemetic profile of Y-25130, a new selective 5-HT3 receptor antagonist.

Y-25130( (+/-)N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro-4-methyl-3-oxo-3,4-dihydro - 2H-1,4-benzoxazine-8-carboxamide hydrochloride) is a potent and selective 5-HT3 receptor antagonist free of dopamine receptor blocking activity. This compound was effective against emesis induced in animals by cytotoxic drugs or by total body X-radiation. When given prophylactically, the doses required to completely inhibit cisplatin-induced emesis in dogs and doxorubicin and cyclophosphamide-induced emesis in ferrets were 0.1 and 0.3 mg/kg i.v., respectively. Y-25130, at the dose of 0.3 mg/kg i.v., almost completely inhibited X-radiation-induced emesis in ferrets. When given during emesis, the doses required to completely inhibit cisplatin-induced emesis in dogs and doxorubicin- and cyclophosphamide-induced emesis in ferrets were 0.1 and 0.3 mg/kg i.v., respectively. The i.v. dose of 0.3 mg/kg of Y-25130 was enough to almost completely inhibit cisplatin-induced emesis in dogs for 24 h. From these results, it is suggested that Y-25130 may become an effective antiemetic drug against emesis induced by anticancer therapy.

Animals↗

Antidopaminergic effects of the stereoisomers of N-[(1-alkyl-2- pyrrolidinyl)methyl]-5-sulfamoylbenzamides and -2,3-dihydrobenzofuran-7-carboxamides.

The stereoisomers of some N-[(1-alkyl-2-pyrrolidinyl)methyl]-5- sulfaoylbenzamides (3-8) and -2,3-dihydrobenzofuran-7-carboxamides (9-18) were prepared to compare their dopamine D2 receptor binding affinities (in vitro) and inhibitory effects on apomorphine-induced hyperactivity (in vivo). In the 1-ethyl substituted compounds of the two series, the stereoisomers with S absolute configuration at the 2-position of the pyrrolidine moiety (S enantiomer 3 and 2S diastereomers 9 and 10) were more potent in both of the above activities than those with R absolute configuration (R enantiomer 4 and 2R diastereomers 11 and 12, respectively), whereas the R enantiomer (8) was more potent than the S enantiomer (7) in the 1-n-hexyl-substituted-benzamides and the 2R diastereomers (15, 16, and 18) were more potent than the 2S diastereomers (13, 14, and 17) in the 1-n-butyl- and 1-n-hexyl-2,3-dihydrobenzofuran-7-carboxamides. It was found that the stereospecificity of the compound activities altered from the S configuration to the R configuration as the 1-alkyl side chain became longer in the two series. How these stereoisomers meet the configurational requirements to interact with the dopamine D2 receptors is also discussed.

Animals↗

Striatal blood flow, glucose metabolism and 18F-dopa uptake: difference in Parkinson's disease and atypical parkinsonism.

Striatal blood flow, glucose metabolism and 18F-Dopa uptake were studied with positron emission tomography (PET) in eight non-demented patients with idiopathic Parkinson's disease and eight with atypical Parkinsonism. Patients with atypical Parkinsonism had no specific cause for the Parkinsonian symptoms and were clinically different from Parkinson's disease with lack of resting tremor and a poor response to dopaminergic drugs. Decreased 18F-Dopa uptake in the putamen was observed in patients with Parkinson's disease and atypical Parkinsonism compared with normal controls. 18F-Dopa uptake in the head of the caudate was also significantly reduced in both conditions but relatively less in Parkinson's disease. Decreased blood flow and glucose metabolism in the striatum associated with a global cerebral decrease were also observed in patients with atypical Parkinsonism compared with controls, while they were preserved in patients with Parkinson's disease, indicating affected neurons not only in the striatum but also in the cerebrum in patients with atypical Parkinsonism compared with patients with Parkinson's disease. The differences in the caudate 18F-Dopa uptake, and blood flow and glucose metabolism in the cerebrum including the striatum between Parkinson's disease and atypical Parkinsonism assessed by PET may be due to the differences in the pathophysiological mechanism between Parkinson's disease and atypical Parkinsonism.

Adolescent↗

Studies on the synthesis of condensed pyridazine derivatives. IV. Synthesis and anxiolytic activity of 2-aryl-5,6-dihydro-(1)benzothiepino[5,4- c]pyridazin-3(2H)-ones and related compound.

A series of 2-aryl-5,6-dihydro-(1)benzothiepino[5,4-c]pyridazin-3(2H)- ones and related compounds were synthesized and evaluated for their ability to displace 3H-diazepam from rat brain membranes in vitro, and to prevent bicuculline induced convulsions in mice in vivo. Compounds with a 4'-methoxyphenyl (36) or 4'-chlorophenyl group (37, 39--42) as 2-aryl substituents showed prominent activities in both the in vitro and in vivo tests. Among them, 2-(4'-chlorophenyl)-5,6-dihydro- (37) and 2-(4'-chlorophenyl)-5,6-dihydro-10-fluoro-(1)benzothiepino[5,4-c]+ ++pyridazin- 3(2H)-one 7-oxides (41) showed activity twice as potent as diazepam in an anticonflict test (Vogel type, rats) while exhibiting less muscle relaxation (rotarod test, mice) and augmentation of gamma-aminobutyric acid-induced chloride current (Icl) in isolated frog sensory neurones than diazepam. Compound 37 (Y-23684) was selected from this series as a candidate for further development. The structure-activity relationships are discussed.

Animals↗

GABA distribution in the central vestibular system after retroauricular galvanic stimulation. An immunohistochemical study.

The changes of the neurotransmitter (GABA) distribution in the brain stem of rats by retroauricular galvanic stimulation were investigated using the immunohistochemical method. In the lateral vestibular nucleus GABA-like immunoreactivity was more intensive on the side ipsilateral to the anodal stimulation than on the other side. It is concluded that retroauricular galvanic stimulation causes some changes in the inhibitory activity of the lateral vestibulo-spinal tract and of the spinal motor neuron.

Animals↗