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Biomedical subjects

S Sakata

Publications and source records attributed to S Sakata.

At least 91 records · Page 5Linked to original sources

Metabolic fate of [3H]1-beta-D-arabinofuranosyl-5-[(E)-2-bromovinyl]uracil in herpes simplex virus type 1-infected cells.

The metabolic fate of 1-beta-D-arabinofuranosyl-5-[(E)-2-bromovinyl]uracil (BV-araU) in herpes simplex virus type 1-infected cells was studied using tritium-labeled BV-araU. [3H]BV-araU was selectively taken-up by infected cells. Approximately 10% of the total uptake of [3H]BV-araU was recovered from the acid-insoluble fraction at any time post-infection. Both cellular uptake of [3H]BV-araU and its incorporation into the acid-insoluble fraction increased with increasing incubation time through 8 hr post-infection. Uptake of [3H]BV-araU and its incorporation into the acid-insoluble fraction also increased proportionally to the duration of exposure to [3H]BV-araU. An alkaline sucrose gradient sedimentation analysis revealed that the radioactive DNA obtained from cells pulse-labeled with [3H]BV-araU were small DNA fragments which remained at the top following a chasing period in isotope-free medium, whereas that pulse-labeled with [3H]thymidine was chased to a fraction of high molecular weight DNA. Nuclease P1 digestion reduced 99% of the [3H]BV-araU-labeled DNA extracted from infected cells to a low molecular weight. Following digestion of [3H]BV-araU-labeled DNA with micrococcal nuclease and spleen exonuclease, all of the radioactivity was recovered as [3H]BV-araU 3'-monophosphate. Thus, BV-araU strongly inhibits the elongation of viral DNA strands as demonstrated by the alkaline sucrose gradient sedimentation analysis, whereas at least a portion of the [3H]BV-araU is incorporated inside viral DNA strands in infected cells.

Acyclovir↗

Effect of blood blow and haematocrit on the relationship between muscle venous PO2 and oxygen uptake in dog maximally contracting gastrocnemius in situ.

1. To clarify the limiting factors for peak VO2 (VO2,peak), we measured muscle venous PO2, (PVO2) and VO2,peak under various O2 delivery conditions (arterial O2 concentration x flow) via the alteration of blood flow and haematocrit (Hct) in anaesthetized dog gastrocnemius muscle (n = 11) stimulated by 1 Hz isometrically and tetanically. 2. Two levels of flow (high and moderate) were maintained by using a pump (150 and 100 mL/min per 100 g, respectively). Haematocrit was adjusted to 45 and 30% by isovolaemic haemodilution with dextran (MW 40,000). 3. The decrease in Hct induced a 31% decrease in O2 delivery (P < 0.05), a 9-12% decrease in PVO2, a 23% decrease in VO2,peak (P < 0.05) and a 12-14% increase in O2 extraction (VO2/O2 delivery) at both flow levels. The decrease in flow induced a 24-25% decrease in O2 delivery (P < 0.05), a 15-17% decrease in PVO2 (P < 0.05), a 9% decrease in VO2,peak (P < 0.05) and a 19-22% increase in O2 extraction (P < 0.05) at both Hct levels. 4. The results suggest that the limiting factor of VO/,peak, unrelated to O2 diffusion limitation (i.e. the change in the heterogeneity of VO2 to O2 delivery ratio among capillaries), due to lowering Hct may be different from that due to lowering blood flow in maximally contracting muscle.

Animals↗

[A case of bacterial meningitis induced by strongyloidiasis].

A 75-year-old female with diabetes mellitus, who was born and lived in West north Kyusyu, was admitted to our hospital, because of unconsciousness and loss of appetite. The physical examination showed neck stiffness and a high fever. The laboratory data showed accentuation of inflammatory reaction and azotemia and positive HTLV-1 antibody. The spinal fluid showed increase of cell count and amount of protein. A stool and sputum smear revealed rhabditis form larvae of the nematode. Antibiotics and ivermectin were administered for the bacterial meningitis and hyperinfection of the strongyloides, respectively. Consequently, meningitis and strongyloidiasis improved. It was considered that the patient was infected with strongyloides from her husband who serve in the army during World-War II, and hyperinfection of strongyloides resulted from the immunosuppressive state of diabetes mellitus. Ivermectin, and anti-strongyloides agent, was effective, and no side effects were seen. However, the therapeutic resistance in this case was associated with the positive HTLV-1 antibody.

Aged↗

Spectral characteristics of ventricular response to atrial fibrillation.

To investigate the spectral characteristics of the fluctuation in ventricular response during atrial fibrillation (AF), R-R interval time series obtained from ambulatory electrocardiograms were analyzed in 45 patients with chronic AF and in 30 age-matched healthy subjects with normal sinus rhythm (SR). Although the 24-h R-R interval spectrum during SR showed a 1/f noise-like downsloping linear pattern when plotted as log power against log frequency, the spectrum during AF showed an angular shape with a breakpoint at a frequency of 0.005 +/- 0.002 Hz, by which the spectrum was separated into long-term and short-term components with different spectral characteristics. The short-term component showed a white noise-like flat spectrum with a spectral exponent (absolute value of the regression slope) of 0.05 +/- 0.08 and an intercept at 10(-2) Hz of 4.9 +/- 0.3 log(ms2/Hz). The long-term component had a 1/f noise-like spectrum with a spectral exponent of 1.26 +/- 0.40 and an intercept at 10(-4) Hz of 7.0 +/- 0.3 log(ms2/Hz), which did not differ significantly from those for the spectrum during SR in the same frequency range [spectral exponent, 1.36 +/- 0.06; intercept at 10(-4) Hz, 7.1 +/- 0.3 log(ms2/Hz)]. The R-R intervals during AF may be a sequence of uncorrelated values over the short term (within several minutes). Over the longer term, however, the R-R interval fluctuation shows the long-range negative correlation suggestive of underlying regulatory processes, and spectral characteristics indistinguishable from those for SR suggest that the long-term fluctuations during AF and SR may originate from similar dynamics of the cardiovascular regulatory systems.

Adult↗

Oxygen uptake in maximally contracting muscle perfused at low flow with high O2 affinity erythrocytes.

To analyze the roles of blood flow and blood-tissue diffusion in determining oxygen (O2) availability to maximally exercising skeletal muscle, we investigated the influence of low flow on the O2 uptake (VO2)-venous PO2 (PVO2) relation with normal and high O2 affinity erythrocytes. We prepared normal and high O2 affinity erythrocytes by incubating human citrate-phosphate-dextrose-stored erythrocytes with and without cyanate. We perfused maximally contracting gastrocnemius muscle at 4-Hz isometric twitch with solutions containing normal and high O2 affinity erythrocytes for 3 min in anesthetized dogs. During stimulation, perfusion flow was maintained low at 50 ml.min-1.100 g-1 with a perfusion pressure of 50 mmHg. PVO2 for normal affinity erythrocytes (25.6 Torr) was significantly (p < 0.05) higher than that for high O2 affinity erythrocytes (15.9 Torr). Nevertheless, the VO2 for normal and high O2 affinity erythrocytes was approximately the same value, 6.5 ml.min-1.100 g-1 (p > 0.05). The O2 extraction rate was approximately 80% in normal and high O2 affinity erythrocytes. These results indicate that VO2 at low flow was independent of PVO2 in maximally contracting skeletal muscle, although PVO2 was reversely correlated with O2 affinity. We suggest that this PVO2-independency of VO2 at low flow is caused by long red-cell transit time in the capillary without diffusion-limitation and/or a 20% constant arterio-venous shunt of arterial O2 delivery.

Animals↗

Cosinor analysis of feed intake cycle of rats fed a zinc-deficient diet and the effect of zinc supplementation.

Rats fed a Zn-deficient diet develop a characteristic cyclic variation in feed intake (Mills et al., Am J Clin Nutr 22: 1240-1249 (1969). A preliminary analysis (Tamaki et al., Br J Nutr 73: 711-722 (1995)) of the cyclic variations was followed with a personal computer. Cosinor analysis revealed that the cyclic period of the feed intake of male rats was 3.5 +/- 0.05 d. The mesor, amplitude and acrophase value were 10.0 +/- 0.3 g/d, 4.4 +/- 0.2 g/d and 3.5 +/- 0.3 radian, respectively. The cycle of body-weight change of the Zn-deficient rats was well synchronized with that of feed intake. The parameters of the feed intake cycle had a high correlation to the corresponding parameters of body-weight change (mesor: r = 0.846; amplitude: r = 0.771; period: r = 0.925; acrophase: r = 0.452). With the supplementation of Zn (0.95-3.80 mg/kg of the Zn-deficient diet), cyclic variations in feed intake and body-weight change were also found. The mesor, amplitude and period of feed intake cycle were is good correlation with Zn intake (r = 0.856, p < 0.001, r = 0.804, p < 0.001 and r = 0.613, p < 0.01, respectively). The cycle of feed intake of the rats fed a Zn-free diet was simulated to be: mesor 9.7 +/- 0.1 g/d, amplitude 6.5 +/- 0.1 g/d and period 3.4 +/- 0.02 d. The concentration of Zn intake given the half-maximal value of the amplitude was assumed to be 56 +/- 1 microgram/d.

Alkaline Phosphatase↗

[T4 lung cancer: surgical indications based on results of surgical treatment].

During the period of 1981 and 1995, 54 patients with T4 lung cancer underwent pulmonary resection in our institutes. The actuarial survival rate of them was 30% at three years and 12% at five years. The five-year survival rate of 12 patients with complete resection was 33%. On the other hand, the five-year survival rate of 30 patients with incomplete resection was 9%. The five-year survival rates of 17 patients with N0 disease, 9 patients with N1 disease, and 22 patients with N2 disease were 13%, 40%, and 5%, respectively. There was a significant difference in survival between patients with N1 and N2 disease. Four patients survived for more than five years after the operation : two patients had invasion to the left atrium and two had a slight degree of pleural dissemination. Radical pulmonary resection may yield long-term survival in T4 lung cancer patients having invasion to the left atrium.

Adenocarcinoma↗

[First example of Hb lepore Washington-Boston trait in a Japanese].

An abnormal hemoglobin (Hb) found in a 63-year-old Japanese woman presenting with asymptomatic chronic microcytic anemia was extensively characterized by the conventional protein chemistry, restriction mapping of the genomic DNA with Bgl II digestion, and direct sequencing of a relevant segment of the mutant non-alpha-globin gene. The results identified a hybrid globin with delta- and beta-like sequences, from position 1 to 87 and from 105 to 146 (C-terminal), respectively. The delta beta fusion gene was produced by deletion of 7.4 kb involving parts of the two closely linked genes. The break point was somewhere within the homologous 58 bps, from codon 88 to IVS-II-7. The same deletion had repeatedly been reported in Hb Lepore Washington-Boston. The expression of a mild (delta beta)(+)-thalassemia trait in the present case completely agreed with previous reports on representative Hb Lepore heterozygotes. The basis for the activity of Hb Lepore gene which is several times higher than the delta-globin gene was discussed.

Asian People↗

Availability of nasal mask BiPAP systems for the treatment of respiratory failure after cardiovascular surgery.

BACKGROUND: The availability of nasal mask bi-level positive airway pressure (BiPAP) support in managing respiratory failure following cardiovascular surgery was studied. MATERIALS AND METHODS: BiPAP support was used for eight patients requiring postoperative prolonged respiratory support of 72 hours or longer. Their mean age was 65 years of age and the mean periods of postoperative endotracheal intubation was 12+/-5 days. BiPAP support was removed within 48 hours in six out of eight patients. Reintubation of an endotracheal tube was not necessary in all eight patients after the BiPAP treatment. RESULTS: The respiratory rates during the BiPAP management remained unchanged. The values of the respiratory index significantly (p<0.01) improved after BiPAP management (1.5+/-0.2 --> 0.9+/-0.2). A-aDO2 and Qs/Qt decreased (p<0.1) after the BiPAP management. There were no significant differences in central venous pressure and circulatory states during BiPAP support. CONCLUSIONS: In conclusions, BiPAP support is a noninvasive management technique for postoperative respiratory failure and may also prevent prolonged endotracheal intubation.

Aged↗

Synthesis of 2'-deoxy-2'-fluoro-4'-thioarabinonucleosides using the Pummerer rearrangement and their biological evaluation.

Searching for more effective antineoplastic and antiviral agents, we have prepared various 2'-deoxy-2'-fluoro-4'-thioarabinonucleosides. The glycosylation reaction of persilylated pyrimidine bases with a 4-thiosugar derivative was performed using SnCl4 as a catalyst. The same reaction between purines and the 4-thiosugar, catalyzed by TMSOTf, gave the corresponding purine 4'-thionucleosides. Pyrimidine derivatives (e.g., 5-ethyluracil, 5-iodouracil, and 5-iodocytosine) showed potent anti-HSV-1 activities, and guanine and 2,6-diaminopurine derivatives showed marked anti-HCMV activities.

Antimetabolites, Antineoplastic↗

A novel gene family defined by human dihydropyrimidinase and three related proteins with differential tissue distribution.

We have isolated cDNA clones encoding dihydropyrimidinase (DHPase) from human liver and its three homologues from human fetal brain. The deduced amino acid (aa) sequence of human DHPase showed 90% identity with that of rat DHPase, and the three homologues showed 57-59% aa identity with human DHPase, and 74-77% aa identity with each other. We tentatively termed these homologues human DHPase related protein (DRP)-1, DRP-2 and DRP-3. Human DRP-2 showed 98% aa identity with chicken CRMP-62 (collapsin response mediator protein of relative molecular mass of 62 kDa) which is involved in neuronal growth cone collapse. Human DRP-3 showed 94-100% aa identity with two partial peptide sequences of rat TOAD-64 (turned on after division, 64 kDa) which is specifically expressed in postmitotic neurons. Human DHPase and DRPs showed a lower degree of aa sequence identity with Bacillus stearothermophilus hydantoinase (39-42%) and Caenorhabditis elegans unc-33 (32-34%). Thus we describe a novel gene family which displays differential tissue distribution: i.e., human DHPase, in liver and kidney; human DRP-1, in brain; human DRP-2, ubiquitously expressed except for liver; human DRP-3, mainly in heart and skeletal muscle.

Amidohydrolases↗

Cell kill kinetics of an antineoplastic nucleoside, 1-(2-deoxy-2-methylene-beta-D-erythro-pentofuranosyl)cytosine.

The cytotoxic properties of 1-(2-deoxy-2-methylene-beta-D-erythro-pentofuranosyl)cytosine (DMDC) were compared with those of 1-beta-D-arabinofuranosylcytosine (ara-C), using SK-MEL-28(P-36) human melanoma cells. DMDC and ara-C were most cytotoxic to cells in the S phase of the cell cycle. Cell cycle progression in S phase was blocked by both compounds. Treatment with DMDC (1 microgram/mL) or ara-C (1 and 30 micrograms/mL) did not increase cytotoxicity against asynchronous cells when the exposure time was prolonged from 1 to 6 hr, but did increase cytotoxicity thereafter. These findings suggest that cells in S phase are rapidly killed by the treatment but are temporarily prevented or delayed entry into the drug-sensitive S phase. On the other hand, DMDC treatment at a higher concentration (30 micrograms/mL) increased cytotoxicity in a time-dependent manner. Intracellular DMDC 5'-triphosphate (DMDCTP) increased in proportion to exogenous DMDC concentration, which was not saturated by treatment with a maximum concentration of the compound at 80 micrograms/mL. In contrast, intracellular ara-C 5'-triphosphate reached peak level when the cells were treated with ara-C at 8 micrograms/mL. The cytotoxicity of DMDC treatment for 4 hr increased relative to the intracellular DMDCTP accumulated during the period. These findings suggest that in cells treated with DMDC at a high concentration, an effective DMDCTP level is maintained for an extended period after washing out the compound from the medium. Consequently, the cells would be killed in the same way as in the case of extended exposures over 6 hr to DMDC at low concentration or to ara-C, in addition to acute S-phase-specific cytotoxicity.

Antineoplastic Agents↗

Molecular cloning and sequencing of a cDNA encoding dihydropyrimidinase from the rat liver.

A cDNA encoding dihydropyrimidinase has been isolated from a rat cDNA library. The N-terminal and an internal amino acid sequences were determined, and PCR primers were designed based on these sequences. Using a cDNA fragment amplified by RT-PCR with these primers, three cDNA clones were isolated from a rat liver library. The clone with the longest insert of 2129 bp contained a 1557 bp open reading frame encoding a polypeptide of 519 residues with a molecular mass of 56,832 Da.

Amidohydrolases↗

The effect of cyclosporin A administration on bone metabolism in the rat evaluated by biochemical markers.

We investigated the effects of cyclosporin A (CsA), an immunosuppressive agent, on bone remodeling in 6 rats compared to 6 controls, using a histomorphometric technique and biochemical markers for bone metabolism. With an oral daily dose of 15 mg CsA/kg of body weight for 28 days, the trabecular bone volume in CsA administered rats was significantly lower than that in control rats, which indicates bone loss in CsA rats. In CsA rats, bone resorption increased, and urinary pyridinoline (Pyr) significantly increased on day 28 compared with control rats. In contrast, bone formation assessed by serum osteocalcin and osteoid volume had no remarkable changes. These results suggest that administration of CsA for 28 days induces bone loss due to uncoupling between bone resorption and bone formation.

Administration, Oral↗

Mixed disulphide formation in myoglobin of mouse (Mus musculus).

The myoglobin, isolated from murine skeletal muscles by chromatofocusing, showed the three components, one major and two minor, with different electrophoretic mobilities. The major component with the isoelectric point (pI) of 7.55 had one reactive SH/mole, while the others with pI of 7.32 and 7.16 showed none, which could be rendered fully reactive by treating the proteins with beta-mercaptoethanol. The three components were the same in their molecular weight (18 kDa), amino-acid composition with one Cys residue and oxygenation properties. By a sensitive high-performance liquid chromatography method, the occurrence of cysteine or glutathione mixed disulphide was verified in the two minor components. We conclude from these results and incubation experiments with low-molecular-weight thiols that the two minors were derived from the major by a mixed disulphide formation with either cysteine or glutathione of the cysteinyl SH at the 66th sequence.

Animals↗

Differences in response of thyrotropin to 3,5,3'-triiodothyronine and 3,5,3'-triiodothyroacetic acid in patients with resistance to thyroid hormone.

This study investigated the response of TSH secretion to 3,5,3'-triiodothyronine (T3) and 3,5,3'-triiodothyroacetic acid (Triac) in patients with resistance to thyroid hormone, and compared the responses with those in patients with TSH-secreting pituitary adenoma and normal subjects. A short-term administration of 75 microg of T3 daily for 7 days suppressed serum TSH concentrations almost completely in normal subjects, but suppressed TSH only partially in patients with resistance to thyroid hormone and TSH-secreting pituitary adenoma. A single-dose administration of 75 microg of T3 gave similar results in regard to TSH suppressibility in these three subjects groups. In contrast, a single-dose administration of 1.4 mg of Triac remarkably suppressed serum TSH concentrations after 2 hours in not only normal subjects (-34 +/- 11% [mean +/- SD] from the basal value) but also in patients with resistance to thyroid hormone (-31 +/- 9%), and this TSH suppression continued for 4 hours. After 24 hours, this TSH suppression persisted in normal subjects (-62 +/- 12%) but was relieved in patients with resistance to thyroid hormone (-23 +/- 14%). After the Triac administration, molar ratios of alpha-subunit to TSH in serum were decreased in patients with TSH-secreting pituitary adenoma but increased in patients with resistance to thyroid hormone. Because the Triac therapy for patients with resistance to thyroid hormone suppressed pituitary-TSH secretion during the early phase of drug ingestion, this drug should be given several times within a day to obtain continuous TSH-suppressive effects.

Adenoma↗

Preoperative intra-arterial infusion chemotherapy for invasive thymoma: a case report.

A 24-year-old man was diagnosed as having mixed-type thymoma by preoperative percutaneous needle biopsy. A chest computed tomogram showed a tumor measuring 12x9 cm. Selective intra-arterial infusion chemotherapy was first selected because invasion to the superior vena cava was suspected. Bolus injection of 50 mg/m2 cisplatin and 20 mg/m2 adriamycin was performed once into the right internal thoracic artery. The resulting decrease in tumor size was 81%. Neither complications due to the infusion procedure nor side effects due to the anticancer drugs were encountered. An extended thymectomy with partial resection of the mediastinal pleura was safely performed. The histological diagnosis of the resected tumor was thymic hyperplasia. The patient was transferred to a radiologist for additional radiotherapy. Selective intra-arterial infusion chemotherapy for invasive thymoma is an effective therapy, producing no significant side effects and allowing safe resection.

Adult↗