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Biomedical subjects

K Shiba

Publications and source records attributed to K Shiba.

At least 127 records · Page 7Linked to original sources
PubMed1994

Identification of two new types of S-linked conjugates of Etoc in rat.

1. Two major metabolites of 14C-labelled (4S,1R)-trans-Etoc[(S)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1R)-trans-chrysanthemate] were purified using a combination of chromatographic techniques and identified by spectroanalysis (nmr(HMBC) and FAB-, TSP-MS). These were established as new types of S-linked conjugates (sulphonic acid and mercapturic acid types). 2. To examine the mechanism of formation of the sulphonic acid and mercapturic acid conjugates, sodium sulphate or glutathione labelled with 35S were administered to rat along with unlabelled trans-Etoc. Both sulphonic acid and mercapturic acid conjugates were found in the excreta, more of the former being yielded with 35S-sodium sulphate than with 35S-glutathione, implying that a sulphonic acid was incorporated into the double bond of a possible intermediate after reduction of sulphate to sulphite. The mercapturic acid conjugate was produced only with 35S-glutathione, implying incorporation of glutathione into the triple bond before subsequent generation of mercapturic acid from the glutathione conjugate. 3. Additional investigation of whether or not the mercapturic acid conjugate was produced by mixing the alcohol moiety of Etoc, PGL (4-hydroxy-3-methyl-2-(2-propynyl)cyclopent-2-en-1-one) and N-acetyl-L-cysteine under alkaline conditions. However, spectral data for the synthesized compound were not the same as those of the metabolite generated in vivo. That is, the addition reaction appeared to proceed by anti-Markownikov's rule, whereas the in vivo metabolite was apparently formed according to Markownikov's rule. Addition of glutathione at a triple bond has not been reported to our knowledge for any other foreign compounds in mammalian species.

Animals↗
PubMed1994

[Total aortic root replacement exclusively with full-thickness suturing].

This paper describes two cases of total aortic root replacement using a valved conduit with a side branch. The full-thickness suturing technique was exclusively used at all anastomotic sites, and some technical devices are also presented. The conduit and a Hemashield Woven Double Velour graft used to make it were found very beneficial for the operation of this kind, and our procedure will equally provide every surgeon with a good result.

Aged↗
PubMed1993

Effects of microinjection of a GABA antagonist into the periaqueductal gray upon electrically-induced vocalization in decerebrate cats.

The effects of the GABA antagonist bicuculline methiodide (BIC), microinjected into the ventrolateral periaqueductal gray (PAG) on the stimulus threshold of electrically-induced vocalization were examined in unanesthetized precollicular-postmamillary decerebrate cats. To induce vocalization, repetitive electrical stimulation (0.2 ms, 100 Hz, 5-10 s duration) was delivered to the caudal portion of the PAG (30 to 300 microA) or the pontine call site (PCS) (10 to 60 microA) in the ventrolateral pontine reticular formation. Injection of 0.1 microliter of 2 mM BIC into the caudal portion of the PAG decreased the stimulus thresholds of the PCS and the injection site for about 1 h. Injection of BIC into the reticular formation near the PAG, where the electrical stimulation induced vocalization, did not decrease the stimulus thresholds of the PCS or the injection site. These results indicate that GABAergic inhibition regulates the excitability of the cells within the ventrolateral PAG, which exerts an excitatory effect on the lower brain structures that produce vocalization.

Animals↗
PubMed1993

Time course of dopamine-D2 and serotonin-5-HT2 receptor occupancy rates by haloperidol and clozapine in vivo.

In vivo occupancy of dopamine-D1, D2 and serotonin-5-HT2 receptors by haloperidol 10 mg/kg and clozapine 20 mg/kg were studied. Rats were injected intravenously with [3H]-YM-09151-2, [3H]-SCH23390, or [3H]-ketanserin 10 min after the administration of the tested drugs. Fifteen to 240 min after the ligand injection, the receptor occupancy rates of the drugs in the striatum and frontal cortex were calculated. Clozapine demonstrated the higher 5-HT2 and lower D2 occupancies in the respective regions. A dose-response analysis of D2 and 5-HT2 receptor occupancy by the drugs consolidated the higher 5-HT2 binding affinity of clozapine in comparison with haloperidol. The present methodology may serve as an accurate tool to evaluate the peculiarity of various antipsychotics.

Animals↗
PubMed1993

[Treatment of severe pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA) and Candida krusei with granulocyte colony-stimulating factor (G-CSF): a case report].

A 24-year-old male with chronic renal failure on Continuous Ambulatory Peritoneal Dialysis (CAPD) complained of cough and dyspnea. Chest X-ray film showed a pneumonia shadow and MRSA and Candida krusei were detected in the sputum. Pneumonia improved with vancomycin and fluconazole. Treatment with methylprednisolone was needed for retinodialysis. After this treatment, pneumonia deteriorated. Pneumonia did not improve with vancomycin and anti-fungal agents. This severe pneumonia was improved with a combination therapy of vancomycin, miconazole and G-CSF. A combination therapy of antibiotics and G-CSF is considered to be effective for severe pneumonia.

Adult↗
PubMed1993

[The efficacy of external high frequency oscillation: experience in a quadriplegic patient with alveolar hypoventilation].

External high frequency oscillation (EHFO) around a negative pressure using a thoracoabdominal chamber without an artificial airway has been shown to be an effective form of ventilation in a quadriplegic patient. The patient was an 18 year old male, suffering from high-level cervical cord tumor (lipoma). His respiratory distress was severe, respiration was diaphragmatic only. Because of acute respiratory insufficiency, he was intubated and put on IPPV. Attempts at weaning were not thought to be feasible. Then the Hayek Oscillator was applied with a frequency of 120. After 5 days on the Hayek Oscillator, he was extubated. EHFO was associated with a significant increase in PaO2 and VA, and a significant decrease in PaCO2. It is remarkable that the patient expelled sputum whenever he was connected to the Hayek Oscillator, far beyond that achievable by physiotherapy. EHFO avoids the need for endotracheal intubation, thus reducing the hazards of mechanical ventilation attributable to intubation. We conclude that EHFO produces gas exchange significantly and that this technique may have potential clinical application.

Adolescent↗
PubMed1992

Tripartite functional assembly of a large class I aminoacyl tRNA synthetase.

A 939-amino acid monomeric class I tRNA synthetase has been split into three inactive peptides. The three peptides spontaneously assemble in vivo to reconstitute active protein. Active tripartite complexes were demonstrated in vitro. The tripartite assembly of this synthetase increases by several-fold the size of a polypeptide that has been demonstrated to be assembled from more than two constituent pieces. The results indicate that contemporary single-chain tRNA synthetases or other large proteins could in principle develop from intermediates composed of non-covalent assemblages of multiple peptides.

Amino Acid Sequence↗
PubMed1992

RNA binding determinant in some class I tRNA synthetases identified by alignment-guided mutagenesis.

The N-terminal nucleotide binding folds of all 10 class I tRNA synthetases (RSs) contain characteristic conserved sequence motifs that define this class of synthetases. Sequences of C-terminal domains, which in some cases are known to interact with anticodons, are divergent. In the 676-amino acid Escherichia coli methionyl-tRNA synthetase (MetRS), interactions with the methionine tRNA anticodon are sensitive to substitutions at a specific location on the surface of the C-terminal domain of this protein of known three-dimensional structure. Although four class I synthetases of heterogeneous lengths and unknown structures are believed to be historically related to MetRS, pair-wise sequence similarities in the region of this RNA binding determinant are obscure. A multiple alignment of all sequences of three of these synthetases with all MetRS sequences suggested a location for the functional analog of the anticodon-binding site in these enzymes. We chose a member of this set for alignment-guided mutagenesis, combined with a functional analysis of mutant proteins. Substitutions within two amino acids of the site fixed by the multiple sequence alignment severely affected interactions with tRNA but not with ATP or amino acid. Multiple individual replacements at this location do not disrupt enzyme stability, indicating this segment is on the surface, as in the MetRS structure. The results suggest the location of an RNA binding determinant in each of these three synthetases of unknown structure.

Diphosphates↗
PubMed1992

Functional assembly of a randomly cleaved protein.

The sequence of a 939-amino acid polypeptide that is a member of the aminoacyl-tRNA synthetase class of enzymes has been aligned with sequences of 15 related proteins. This alignment guided the design of 18 fragment pairs that were tested for internal sequence complementarity by reconstitution of enzyme activity. Reconstitution was achieved with fragments that divide the protein at both nonconserved and conserved sequences, including locations proximal to or within elements believed to form critical elements of secondary structure. Structure assembly is sufficiently flexible to accommodate fusion of short segments of unrelated sequences at fragment junctions. Complementary chain packing interactions and chain flexibility appear to be widely distributed throughout the sequence and are sufficient to reconstruct large three-dimensional structures from an array of disconnected pieces. The results may have implications for the evolution and assembly of large proteins.

Amino Acid Sequence↗
PubMed1992

Surgical treatment of metastatic tumors of long bones and the spine.

We have operated on 42 patients with bone metastasis from various primary tumors over the past fourteen years. The number of operated cases of metastasis secondary to thyroid and breast carcinoma was especially high, since patients with such types of cancer have prolonged life expectancies in general. The sites of these operation were as follows: 27 in the spine, 12 in the femur, 2 in the tibia, and 1 in the humerus.

Aged↗
PubMed1992

Insertional disruption of the nusB (ssyB) gene leads to cold-sensitive growth of Escherichia coli and suppression of the secY24 mutation.

The Escherichia coli gene ssyB was cloned and sequenced. The ssyB63 (Cs) mutation is an insertion mutation in nusB, while the nusB5 (Cs) mutation suppresses secY24, indicating that inactivation of nusB causes cold-sensitive cell growth as well as phenotypic suppression of secY24. The correct map position of nusB is 9.5 min rather than 11 min as previously assigned. It is located at the distal end of an operon that contains a gene showing significant homology with a Bacillus subtilis gene involved in riboflavin biosynthesis.

Amino Acid Sequence↗
PubMed1992

Technetium-99m p-iodophenethyldiaminodithiol (DADT-IPE): potential brain perfusion imaging agent for SPECT.

A new ligand, an N-p-iodophenethyl diaminodithiol (DADT-IPE), an anlog of N-isopropyl-p-iodoamphetamine (IMP), was synthesized and subsequently complexed with 99mTc, using stannous chloride as a reducing agent. Two complexes (a and b) were separated from 99mTc-DADT-IPE by high performance liquid chromatography (HPLC). Competitive inhibition studies showed that the IC50 value of DADT-IPE (70 microM) was similar to that of IMP (49 microM). Biodistribution studies of one of the complexes [99mTc-DADT-IPE(a)] in rats showed that 0.65% of the injected dose of the tracer remained in the brain at 5 min after intravenous injection, with 0.53% of the dose remaining in the brain at 60 min post-injection, whereas the corresponding values for the other complex [99mTc-DADT-IPE(b)] were 0.34% dose in the brain at 5 min and 0.28% dose in the brain at 60 min post-injection. The half-life for clearance of 99mTc-DADT-IPE(a) from rat brain was found to be more than 5 h. These results suggested that 99mTc-DADT-IPE(a) has characteristics which are suitable for cerebral perfusion imaging.

Animals↗
PubMed1992

Preparation of 123I-labeled 2'-iodospiperone and imaging of D2 dopamine receptors in the human brain using SPECT.

[123I]2'-ISP was readily prepared using a radioiodine exchange reaction with a radiochemical yield of approx. 50% after HPLC purification. The radiochemical purity of the product was more than 98% and the specific activity was 5.55-11.1 GBq/mumol. Biodistribution studies performed in mice indicated that injection of [123I]2'-ISP with albumin produced a higher gastric uptake and a lower brain uptake than injection of the radioligand in a weakly acidic solution. In addition, toxicity tests performed in mice demonstrated that acute toxic effects would be very unlikely to be encountered if 2'-ISP was used for diagnostic purposes. A preliminary imaging study with [123I]2'-ISP in a healthy human volunteer showed its specific uptake by the basal ganglia, a region of the brain known to have a high density of D2 dopamine receptors.

Animals↗
PubMed1992

Effects of antacids, ferrous sulfate, and ranitidine on absorption of DR-3355 in humans.

This study examined the effects of widely used antacids (aluminum hydroxide, magnesium oxide, and calcium carbonate), ferrous sulfate, and ranitidine on the absorption of a fluorinated quinolone, (-)-(S)-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro- 7H- pyrido-[1,2,3,-de][1,4]benzoxazine-6-carboxylic acid hemihydrate (DR-3355), in healthy male volunteers enrolled in three separate randomized crossover studies. Study 1 used 100-mg doses of DR-3355 and concurrent doses of aluminum hydroxide (1 g) or magnesium oxide (500 mg), while study 2 used DR-3355 (100 mg) and concurrent ferrous sulfate (160 mg) or calcium carbonate (1 g). Study 3 used DR-3355 (100 mg) and concurrent ranitidine (150 mg). Each study included control doses of DR-3355 (100 mg) alone. When aluminum hydroxide, ferrous sulfate, and magnesium oxide were coadministered with DR-3355, the relative bioavailability of DR-3355 was decreased to 56, 81, and 78%, respectively, of that for DR-3355 (100 mg) alone. Urinary excretion of DR-3355 was also significantly decreased by coadministration of these drugs. Thus, the magnitude of the decrease in the area under the concentration-time curve for DR-3355 varied among antacids, and the ranking of their inhibitory effects correlated with previously reported rankings of stability constants for chelate formation. DR-3355 bioavailability was not influenced by the concurrent administration of calcium carbonate and ranitidine, indicating that changes in gastric pH do not affect DR-3355 absorption.

Adult↗
PubMed1992

Effect of antacid on absorption of the quinolone lomefloxacin.

The effect of antacid on the absorption of lomefloxacin (LFLX) in humans was studied. When LFLX was orally administered concomitantly with aluminum- and magnesium-containing antacids under fasting conditions, its level in plasma decreased by one-half and its area under the concentration-time curve was reduced by 40% compared with the levels observed after treatment with LFLX alone. The urinary recovery value also decreased by 40%. No such effects were noted after coadministration of LFLX and a nonmetallic antacid. This study confirmed the existence of chelate complexes of LFLX with Al3+ and Mg2+ and examined the chelating strength. The stability constants of LFLX with Al3+ and Mg2+ were measured and compared with those of ofloxacin and norfloxacin; little difference was observed among them. LFLX was found to bind more strongly with Al3+ than with Mg2+. Further, the existence of chelate formation was proven by 13C-nuclear magnetic resonance spectroscopy. The decrease in the LFLX level in plasma in humans could be explained by a reduced absorption of the Al(3+)- and Mg(2+)-LFLX chelate complexes.

Adult↗
PubMed1992

Effect of probenecid on the pharmacokinetics of DQ-2556, a new 3-quaternary ammonium cephalosporin antibiotic, in humans.

A total of 5 healthy volunteers were enrolled in a crossover study on the dose dependency and the effect of probenecid on pharmacokinetics of DQ-2556. They were administered intravenously 0.5 and 1.0 g of DQ-2556, and 1.0 g of DQ-2556 with oral administration of probenecid. The linearity in pharmacokinetics of DQ-2556 was confirmed up to the dose of 1.0 g. In the case of 1.0 g of DQ-2556 with probenecid treatment, the area under the serum concentration-time curve was larger, and total and renal clearances were less than those in the case of 1.0 g of DQ-2556 alone (by approximately 15% for each parameter, p < 0.01). These results demonstrated that DQ-2556 is secreted in the renal tubule, although it is excreted mainly by the glomerular filtration.

Administration, Oral↗