Biomedical subjects

T Hasegawa

Publications and source records attributed to T Hasegawa.

At least 19 recordsLinked to original sources

PubMed1992

Escherichia coli tRNA(Asp) recognition mechanism differing from that of the yeast system.

Various tRNA transcripts were constructed to study the identity elements of Escherichia coli tRNA(Asp). Base substitutions from G34 to U34 at the first position of the anticodon, and from U35 to A35 at the second, severely impaired the aspartate charging activity. The activity was also decreased, but in a more moderate fashion, by base changes at G2-C71, C36 and C38. Identity nucleotides of tRNA(Asp) are distributed in a different fashion between E. coli and yeast, which occur at the second base pair of the acceptor stem, G10-U25 base pair in the D-stem and 3' half of the anticodon loop.

Anticodon↗

PubMed1992

Potent preventive action of alpha-carotene against carcinogenesis: spontaneous liver carcinogenesis and promoting stage of lung and skin carcinogenesis in mice are suppressed more effectively by alpha-carotene than by beta-carotene.

Although beta-carotene has been considered to be a key cancer preventive agent in green and yellow vegetables, other types of carotenoids, such as alpha-carotene, may also contribute to anticarcinogenic action, since these carotenoids usually coexist with beta-carotene and are detectable in human blood and tissues. In this study, we compared the inhibitory effect of natural alpha-carotene, obtained from palm oil, with that of beta-carotene on spontaneous liver carcinogenesis in C3H/He male mice. The mean number of hepatomas per mouse was significantly decreased by alpha-carotene supplementation (per os administration in drinking water at a concentration of 0.05%, ad libitum) as compared with that in the control group (P < 0.001, Student's t test). On the other hand, beta-carotene, at the same dose as alpha-carotene, did not show any such significant difference from the control group. Furthermore, we also compared the antitumor-promoting activity of alpha-carotene with that of beta-carotene against two-stage mouse lung carcinogenesis (initiator, 4-nitroquinoline 1-oxide; promoter, glycerol). alpha-Carotene, but not beta-carotene, reduced the number of lung tumors per mouse to about 30% of that in the control group (P < 0.001, Student's t test). The higher potency of the antitumor-promoting action of alpha-carotene compared to beta-carotene was confirmed in other experimental systems; e.g., alpha-carotene was also found to have a stronger effect than beta-carotene in suppressing the promoting activity of 12-O-tetradecanoylphorbol-13-acetate on skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated mice. These results suggest that not only beta-carotene, but also other types of carotenoids, such as alpha-carotene, may play an important role in cancer prevention.

4-Nitroquinoline-1-oxide↗

PubMed1992

[Hydralazine-induced enhancement of hyperthermia treatment in vivo].

Hydralazine (Hyd) is a vaso-active drug that significantly affects the nature of blood flow in tumors. As a result, Hyd reduces blood flow and oxygen tension in tumors, causing an increase in the toxic effect of hyperthermia treatment. We investigated enhancement of the anti-tumor effect of hyperthermia by Hyd on SCC-VII tumors in C3H mice. Hyd was administered by intraperitoneal injection, and tumors were heated by water bath. We measured the tumor temperature in animals receiving Hyd by thermocouple. We found no significant change in tumor temperature with Hyd treatment. The effect of Hyd (2.5 mg/kg, 5.0 mg/kg, 7.5 mg/kg) on tumors was evaluated in terms of a growth delay value at which tumor volume reached four-fold. The growth delay values obtained were 6.25 +/- 0.82, 7.14 +/- 0.90, 8.50 +/- 0.98, 9.72 +/- 0.92, and 9.84 +/- 1.3 days for: hyperthermia alone, Hyd of 1.0 mg/kg, 2.5 mg/kg, 5.0 mg/kg, respectively. This effect was independent of the time course of administration of Hyd. These results indicate that Hyd can increase the therapeutic efficacy of hyperthermia treatment. Changes in the microenvironment, such as low pH and tumor hypoxia, induced by arterial embolization may have increased the sensitivity of tumors to heat.

Animals↗

PubMed1992

Effects of alkyl substitutions of xanthine skeleton on bronchodilation.

Structure-activity relationships in a series of 1,3,7-trialkyl-xanthine were studied with guinea pigs. Relaxant actions in the tracheal muscle were increased with alkyl chain length at the 1- and 3-positions of the xanthine skeleton, but decreased by alkylation at the 7-position. Positive chronotropic actions in the right atrium were potentiated with 3-alkyl chain length but tended to decrease with 1-alkylation and diminish by 7-substitution. Consequently, while the 1- and 3-substitutions were equally important for the tracheal smooth muscle relaxation, the substitution at the 1-position was more important than the 3-substitution for bronchoselectivity. The 7-alkylation may be significant to cancel heart stimulation. There were good correlations between the smooth muscle relaxant action and the cyclic AMP-PDE inhibitory activity in 3-substituents and the affinity for adenosine (A1) receptors in 1-, 3-, and 7-substituents. This suggests that not only the cyclic AMP-PDE inhibitory activity but also the adenosine antagonistic activity is important in the bronchodilatory effects of alkylxanthines. Among these xanthine derivatives, 1-butyl-3-propylxanthine and its 7-methylated derivative showed high bronchoselectivity in the in vitro and in vivo experiments compared to theophylline and enprofylline and may be new candidates for bronchodilator.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1992

Anthranilic acid release in adenosine-inhibited cultures of Saccharomyces cerevisiae and its inhibition by thiamin.

Adenosine, at 1 mM concentrations or above, was found to have a fungistatic effect on Saccharomyces cerevisiae. A substance with amethyst fluorescence was detected in the medium of adenosine-inhibited cultures of S. cerevisiae. This compound was isolated and physicochemically identified as anthranilic acid. Both the inhibition of growth and release of anthranilic acid induced by adenosine were abrogated by thiamin or by the pyrimidine portion of thiamin, 2-methyl-4-amino-5-hdroxymethyl-pyrimidine (hydroxymethyl-pyrimidine); the latter was found to restore intracellular thiamin content that had been reduced by adenosine. It was demonstrated that effects of thiamin and hydroxymethylpyrimidine on S. cerevisiae cultured with adenosine resulted from their inhibition of adenosine uptake by growing yeast cells.

Adenosine↗

PubMed1992

Tissue-specific response of estrogen receptor gene expression to estrogen in chick.

We have developed a sensitive assay system by RT (reverse transcription)-PCR(polymerase chain reaction) to detect the low level of chicken estrogen receptor (cER) transcript. Using this system, the differential expression of cER gene in chick tissues was observed. Moreover, we found that the oviduct cER transcript levels in chick was not affected, albeit the remarkable growth of this tissue, by exogenous estrogen. In contrast, estrogen enhanced the hepatic cER transcript level several folds. Thus, the present study clearly showed a novel tissue-specific response of cER gene expression to estrogen in chick.

Animals↗

PubMed1992

Denervation of dopaminergic neurons with 6-hydroxydopamine increases nerve growth factor content in rat brain.

Denervation of dopaminergic neurons by intra nigral injection of 6-hydroxydopamine (6-OHDA) increased nerve growth factor (NGF) content in the cortex and hippocampus, both of which are innervated by cholinergic neurons. The increase continued during an observation period of 0.5-28 days after the lesion. The time course of changes in NGF content was quite different from that of cholinergic neuron denervation. The decreased dopamine content produced in the striatum by 6-OHDA injection was not recovered during the observation period. These results suggest that dopaminergic neuron damage may affect NGF synthesis.

Animals↗

PubMed1992

[Evaluation of thermal damage after hyperthermia on murine experimental tumor by 31P-NMR spectroscopy--correlation between ATP and growth curve].

The possibility of using 31P-NMR spectroscopy (31P-MRS) to estimate the effect of hyperthermic treatment on mouse FM3A tumor was investigated. 1 x 10(6) cells, suspended in saline, were subcutaneously inoculated to the right thigh of C3H mice. For hyperthermic treatment, the tumor-bearing leg was heated by immersing it in a water bath at 44 degrees C for 10, 20 or 30 min. The signal intensities of ATP and Pi of the tumor were measured utilizing the 31P-MRS technique to calculate the ATP/Pi ratio. Immediately after heating, the ATP/Pi ratio decreased markedly. Eighteen hours after hyperthermic treatment, the ratio recovered but was still smaller than the control value, then became almost constant by 24 hours after heating. The ATP/Pi ratio at 24 hours after heating decreased with increased length of heating and was inversely related to tumor regrowth after hyperthermic treatment. We concluded that non-invasive monitoring with 31P-MRS might provide a good indication of the effect of hyperthermic treatment.

Adenosine Triphosphate↗

PubMed1992

In vitro study of E.coli tRNA(Arg) and tRNA(Lys) identity elements.

Various tRNA transcripts were constructed to study the identity elements of E.coli tRNA(Arg) and tRNA(Lys). Exchange of the anticodon of the major tRNA(Arg) from ACG to either CCG or CCU did not result in a significant loss of arginine acceptor activity, whereas not only that to UUU but also that to ACA or ACC decreased the activity. Base substitutions and deletion at A20 also impaired the arginine charging activity by over 50-fold. Arginine charging activity was introduced by either substitution of the anticodon from UAC to ACG in tRNA(Val) or from UUU to UCU in tRNA(Lys). Only a single base substitution at the third position of tRNA(Trp) anticodon (CCA) from A to G also gave rise to arginine charging activity, which was elevated to a comparable level to that of the tRNA(Arg) transcript by an additional A20 insertion. Base substitutions of the major tRNA(Arg) at the discriminator position into pyrimidines led to a decrease by factors of three to four. These data show that the third letter of the anticodon G36 or U36 besides the second letter C35 and the A20 in the variable pocket is responsible for the arginine acceptor identity, to which the discriminator base A73 or G73 contributes in an auxiliary fashion. In contrast to the arginine system, the transcript with the wild-type tRNA(Lys) sequence showed only 140-fold lower lysine charging activity than the native tRNA(Lys), suggesting the involvement of base modifications in recognition. Replacement of the anticodon UUU with not only UCU and UAC but also UUA and UUC seriously affected the lysine acceptor activity, and those with GUU and UUG also decreased by factors of 17 and 5, respectively. Introduction of UUU into the anticodons conferred lysine charging activity upon both tRNA(Val) and tRNA(Arg). Substitution of the discriminator base A73 by any of the other bases decreased the lysine acceptor activity by a factor of ten. These results indicate the involvements of all the three bases of the anticodon and A at the discriminator position in lysine specific aminoacylation.

Anticodon↗

PubMed1992

[MR imaging of hilar cholangiocarcinoma--comparative study with CT].

Magnetic resonance (MR) images of 18 cases of hilar cholangiocarcinoma were evaluated to compare the effectiveness of Gd-DTPA with that of high dose contrast enhancement computed tomography (HCE-CT) in detecting the primary tumor. The primary tumor was demonstrated as having slightly low intensity compared with liver parenchyma and high intensity compared with the dilated bile duct on T1 weighted images. In contrast, MRI using Gd-DTPA, which was carried out in five cases, revealed intense enhancement of the tumor. As the differentiation between cholangiocarcinoma and dilated bile duct was difficult, it was concluded that the use of Gd-DTPA improves the efficacy of MRI in diagnosing cholangiocarcinoma. Gd-DTPA was also effective in differentiating the growth pattern of the tumor: the infiltrating type was demonstrated as thickening of the wall of the bile duct, the polypoid type as a soft tissue mass in the bile duct. Contrast MRI study is effective for the detection of cholangiocarcinoma. It is also expected to be effective in the staging diagnosis of cholangiocarcinoma.

Adenoma, Bile Duct↗

PubMed1992

Identity determinants of E. coli threonine tRNA.

To investigate the identity determinants of E. coli threonine tRNA, various transcripts were prepared by in vitro transcription system with T7 RNA polymerase. Substitutions of the anticodon second letter G35 and the third letter U36 to other nucleotides led to a remarkable decrease of threonine charging activity. Charging experiments with a series of anticodon-deletion transcripts also suggest the importance of the G35U36 sequence. A mutation at either the G1-C72 or C2-G71 base pair in the acceptor stem seriously affected the threonine charging activity. These results indicate that the second and third positions of the anticodon and the first and second base pairs in the acceptor stem are the recognition sites of E. coli tRNA(THR) for threonyl-tRNA synthetase. Discriminator base, A73, is not involved in threonine charging activity.

Base Sequence↗

PubMed1992

Control of drug release with a combination of prodrug and polymer matrix: antitumor activity and release profiles of 2',3'-diacyl-5-fluoro-2'-deoxyuridine from poly(3-hydroxybutyrate) microspheres.

Drug release was controlled by a combination of prodrug and polymer matrix. Prodrugs of 5-fluoro-2'-deoxyuridine with different physicochemical properties were synthesized by esterification with aliphatic acids (propionate, n-butyrate, and n-pentanoate). Microspheres containing these ester prodrugs were prepared with poly(3-hydroxybutyrate) of three molecular weights (65,000, 135,000, and 450,000). The release rates from the spheres depended on both the lipophilicity of the prodrug and the molecular weight of the polymer. Regardless of the polymer, the relative release rates were propionate greater than butyrate greater than pentanoate. The release of butyrate and pentanoate from the spheres consisting of low-molecular-weight polymer (M(r), 65,000) was faster than that from the spheres of higher molecular weight (M(r), 135,000 or 450,000). A single intraperitoneal injection of spheres of the highest molecular weight polymer containing butyrate or pentanoate resulted in higher antitumor effects against P388 leukemia in mice than did free prodrugs given over a period of five consecutive days. The polymer sphere itself showed low toxicity to and good biocompatibility with mice and rats.

Animals↗

PubMed1992

Pharmacokinetics and the effect of probenecid on the renal excretion mechanism of diprophylline.

The mechanism of renal excretion of diprophylline (DPP) and the effect of probenecid on the active transport of DPP in renal tubules were investigated in rats. The concentration of DPP in plasma increased in proportion to the doses of 10, 30, and 60 mg/kg. The pharmacokinetic parameters and the urinary excretion of DPP did not change significantly with the dose. These findings indicate that DPP possesses dose-independent pharmacokinetics. Pharmacokinetic parameters for tubular secretion of DPP, as determined by a single-injection renal clearance method, were 21.25 micrograms/mL for the Michaelis-Menten constant and 102.38 micrograms/min for maximum velocity. Coadministration of probenecid decreased the total body clearance of DPP but did not change in the steady-state volume of distribution of DPP. The effect of probenecid concentration on the steady-state renal clearance of DPP was evaluated by continuously infusing probenecid at various rates. The renal clearance of DPP decreased as the probenecid concentration increased, a result indicating that probenecid inhibits the tubular secretion of DPP. However, probenecid did not inhibit the renal secretion of DPP completely, probably because of the existence of probenecid-insensitive transport systems for DPP in the renal proximal tubule. The Michaelis-Menten constant, maximum velocity, and glomerular filtration rate, as calculated with the competitive inhibition model for renal clearance of DPP, correlated well with estimated values after a single intravenous administration, as described earlier. The competitive inhibition constant of probenecid was 15.86 micrograms/mL.

Animals↗

PubMed1992

The role of anticodon bases and the discriminator nucleotide in the recognition of some E. coli tRNAs by their aminoacyl-tRNA synthetases.

The T7 polymerase transcription system was used for in vitro synthesis of unmodified versions of the E. coli tRNA mutants that insert asparagine, cysteine, glycine, histidine, and serine. These tRNAs were used to qualitatively explore the role of some anticodon bases and the discriminator nucleotide in the recognition of tRNA by aminoacyl-tRNA synthetases. Coupled with data from earlier studies, these new results essentially complete a survey of all E. coli tRNAs with respect to the involvement of anticodon bases and the discriminator nucleotide in tRNA recognition. It is found that in the vast majority of tRNAs both of these elements are significant components of tRNA identity. This is not universally true, however. Anticodon sequences are unimportant in tRNA(Ser), tRNA(Leu), and tRNA(Ala) while the discriminator base is inconsequential in tRNA(Ser) and tRNA(Thr). The significance of these results for origin-of-life studies is discussed.

Amino Acyl-tRNA Synthetases↗

PubMed1992

The majority of the marker chromosomes in Japanese patients with stigmata of Turner syndrome are derived from Y chromosomes.

DNA analyses of 41 individuals with stigmata of Turner syndrome and a 45,X/46,X+mar or 46,X+mar karyotype were carried out. Southern-blot analysis employing 17 Y-specific probes were used to determine whether the marker chromosome was Y-chromosomal in origin. Of the 41 DNA samples from these patients, 23 contained detectable Y-chromosomal DNA. Points of chromosome breakage were distributed over the entire length of the Y long arm. Three individuals, who carry different portions of the Y chromosome, had developed gonadoblastoma. GBY (the gonadoblastoma locus on the Y chromosome) is mapped proximal to DYS132, midway between the 13 Yq loci that we have studied. We also used a polymerase chain reaction technique that could detect 7 loci over the length of the Y chromosome. This technique may be useful for the rapid assessment of marker chromosomes, especially for evaluating the risk of gonadoblastoma.

Blotting, Southern↗

PubMed1992

Postoperative osteomyelitis due to Mycobacterium fortuitum. A case report.

A rare case of osteomyelitis of the tibia caused by Mycobacterium fortuitum which developed after closed intramedullary Küntscher nail fixation is reported. After extraction of the nail, combination therapy with antituberculous drugs, ofloxacin, and interleukin 2 was undertaken and bony union was achieved. Since a bone cyst formed during union, curettage and conventional cancellous bone grafting were performed. The patient is now pain-free even with prolonged weight-bearing. The success of treatment in this case is in contrast to other reports of the disease.

Adolescent↗

PubMed1992

Intra-operative screw trimming in direct screw fixation of the odontoid process fracture--technical note.

For a satisfactory direct screw fixation of fractures of the odontoid process it is necessary to use a screw of the proper total length and thread length, but such an optimal ready-made screw is not always available. The authors describe a technique of intra-operative screw trimming using a high-speed diamond drill. This adjustment is easily and quickly performed. It enables the screw to act as a compression screw, which facilitates fusion of the fractured surfaces.

Bone Screws↗

PubMed1992

Direct skull marking for a pre-operative localization in regional cerebral surgery. Technical note.

A method is described in which an open neurosurgical target is pre-operatively marked on the skull of a patient. A target point of the scalp surface localized from neuroimaging studies is transferred onto the skull by an injection of pyoktanin blue. Its accuracy and reliability is far superior than that of the usual scalp marking. The method is simple, practical, and allows a smaller, regional craniotomy with the advantage of minimum operative invasiveness.

Adult↗