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Biomedical subjects

A Sakai

Publications and source records attributed to A Sakai.

At least 217 records · Page 12Linked to original sources
PubMed1993

Tumor necrosis factor acts as a tumor promoter in BALB/3T3 cell transformation.

Tumor necrosis factor (TNF), a cytokine, and okadaic acid, a tumor promoter, strongly phosphorylated the same proteins, vimentin and heat shock protein 27, although their time courses were different. Human TNF-alpha at a concentration of 0.6 nM markedly stimulated transformation of BALB/3T3 cells initiated with 3-methylcholanthrene. The human TNF-alpha was about 1000 times more effective than the chemical tumor promoters, okadaic acid and 12-O-tetradecanoylphorbol-13-acetate. TNF induced growth of v-Ha-ras transfected BALB/3T3 cells (Bhas 42 cells), whereas it did not induce growth of nontransfected BALB/3T3 cells. Okadiac acid induced mouse TNF-alpha from Bhas 42 and BALB/3T3 cells. The results suggest that a chemical tumor promoter induces the secretion of TNF-alpha from various cells. The TNF then acts as an endogenous tumor promoter in vivo.

3T3 Cells↗
PubMed1993

Deacylation-reacylation cycle: a possible absorption mechanism for the novel lymphotropic antitumor agent dipalmitoylphosphatidylfluorouridine in rats.

Dipalmitoylphosphatidylfluorouridine (DPPF) is a potent antitumor agent that selectively gains access to the lymphatic system. To determine whether DPPF enters the lymph in an unmodified form, we administered DPPF orally to rats and analyzed lymph collected from a cannula in the thoracic duct. Although lymph was found to contain only very low levels of DPPF, two congeners of DPPF were detected at high levels. Instrumental analysis demonstrated that these congeners are 1-palmitoyl-2-arachidonoylphosphatidylfluorouridine (PAPF) and 1-palmitoyl-2-linoleoyl-phosphatidylfluorouridine (PLPF). PAPF and PLPF levels in thoracic lymph were shown to be approximately 30 times higher than those in plasma. These results suggest that DPPF is absorbed from the intestinal tract via the deacylation-reacylation cycle for the uptake of phospholipids and is selectively delivered to the lymphatic route after oral administration. DPPF is a candidate drug for the treatment of tumor metastasis, especially in cases where metastasis has occurred via the lymphatic route.

Acylation↗
PubMed1993

Effects of continuous infusion of nitroglycerin on pulmonary hemodynamics, lung lymph balance, and prostanoid products in the response to endotoxin in awake sheep.

We examined the effects of continuous intravenous infusion of nitroglycerin (NTG) on lung dysfunction induced by endotoxemia in awake sheep chronically instrumented with lung lymph fistula. We measured the responses of hemodynamics, lung lymph balance, and thromboxane (Tx)B2 and 6-keto-prostaglandin (PG) F1 alpha levels in plasma and lung lymph to endotoxin administration (1 microgram/kg, intravenously [IV], over 30 min) with and without continuous infusion of NTG (1 microgram/kg/min). Continuous infusion of NTG alone (n = 5) over 5 hr did not significantly alter systemic, pulmonary hemodynamics, and/or lung lymph fluid filtration. Infusion of endotoxin alone (n = 7) caused remarkable increases in pulmonary artery pressure (Ppa) and lung lymph flow (Qlym) in the early phase. Continuous infusion of NTG (n = 6) significantly prevented the early increases in Ppa and Qlym after endotoxin. The increased values of TxB2 and 6-keto-PGF1 alpha in both plasma and lung lymph after endotoxemia showed the same increases in groups with and without NTG. These findings suggest that the reduction of pulmonary artery pressure induced by NTG decreased the filtration of fluid into the lungs associated with endotoxemia in sheep, and that the mechanism of vasodilating action of NTG is not due to modifications of constrictive-dilated cyclo-oxygenase products of arachidonate, such as TxA2 and PGI2.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Effects of high altitudes on finger cooling test in Japanese and Tibetans at Qinghai Plateau.

The influences of both hypobaric hypoxia and cold on peripheral circulation were studied using the finger cooling test (measurement of the decrease in finger temperature, measured at the dorsal surface of the finger, during immersion of the hand in 0 degrees C water for 20 min) at Qinghai Plateau. The same test was carried out at simulated altitudes in a 25 degrees C climatic chamber to separate the hypobaric hypoxia influence from that of cold. In Japanese subjects at Qinghai Plateau there was a significant difference between finger skin temperatures (FSTs) during 20 min of 0 degrees C water immersion at altitudes of 2260 m and 4860 m by ANOVA. Mean finger skin temperature during the 20-min immersion (5-20 min, MST) measured at 4860 m was significantly lower than that at 2260 m. In Tibetan subjects, there was also a significant difference between FSTs at 2260 m and at 4860 m by ANOVA. MST at 4860 m tended to be lower than that at 2260 m. In the 25 degrees C climatic chamber, there was a significant difference between FSTs of Japanese expedition members at 2000 m and at 4000 m by ANOVA. MST was higher at 4000 m than at 2000 m, contrary to the data obtained in Qinghai. In conclusion, the higher skin temperature in response to local cold immersion, which would have been caused by stronger hypobaric hypoxia, must have been masked by the lower ambient temperature.

Acclimatization↗
PubMed1993

Expressions of DNA topoisomerase I and II gene and the genes possibly related to drug resistance in human myeloma cells.

In order to clarify the mechanism of drug resistance in human myeloma cells, we investigated the expressions of DNA topoisomerase I and topoisomerase II gene and the genes possibly related to drug resistance; multi-drug resistant gene 1 (MDR-1), glutathione S-transferase class pi gene (GST-pi), by Northern blotting. Myeloma cells in eight of 15 cases prior to chemotherapy expressed topoisomerase I mRNA considerably, while the expression of topoisomerase II mRNA was detected weakly in only one of 16 myeloma patients. There was not any correlation between expression of topoisomerase I mRNA and clinical drug resistance. Significant expression of MDR-1 mRNA and P-glycoprotein was not detected in 25 cases of multiple myeloma prior to chemotherapy and even after several courses of VAD (vincristine, adriamycin and dexamethasone) therapy by Northern blotting and immunostaining using monoclonal anti-P-glycoprotein antibody (MRK-16), respectively. On the other hand, 16 of 21 myeloma cases showed significant expression of GST-pi protein and GST-pi mRNA with the various strengths, but there was no apparent correlation between GST-pi mRNA expression and clinical response. Therefore these data suggest that expression of the genes we tested may not determine the level of drug resistance in multiple myeloma, but lower or no significant expression of topoisomerase II mRNA in most myeloma cells indicates the possibility that topoisomerase II inhibitors such as VP-16 and topoisomerase II-mediated cytotoxic drugs such as adriamycin, are not so effective for the treatment of multiple myeloma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Time-dependently enhanced pressor responses in rat lungs after chronic exposure to high altitude.

To investigate the de-acclimatization process with respect to pulmonary vasoreactivity after high-altitude exposure, we performed a study of changes in pressor responses over time in salt-perfused lungs from rats that had been exposed to high altitude (HA, n = 41, 20 weeks at actual 2400 m). Comparisons were made with the lungs of rats kept at low altitude (n = 8, kept at 610 m). We studied HA rats from the time just after removal from high altitude to 2 weeks after the exposure. The pressor responses of HA lungs to both 0.5 microgram-angiotensin II and 5 min airway hypoxia (3% O2) just after the exposure did not differ from those of controls, but their responses began to increase within 12 h, and reached a maximum 3 days after exposure ended. The increase was time-dependent. We conclude that pulmonary vasopressor responses are enhanced time-dependently during the very early stages of de-acclimatization after high-altitude exposure.

Altitude↗
PubMed1993

Biochemical and immunochemical study of seven families with 3-ketothiolase deficiency: diagnosis of heterozygotes using immunochemical determination of the ratio of mitochondrial acetoacetyl-CoA thiolase and 3-ketoacyl-CoA thiolase proteins.

The possibility of identifying heterozygotes of 3-ketothiolase deficiency, an inborn error of metabolism caused by a defect of mitochondrial acetoacetyl-CoA thiolase (T2), was tested in seven unrelated families by using enzymatic assay of thiolase activity and immunoblot analysis. The ratio of acetoacetyl-CoA thiolase activities, in the presence and absence of K+ ion (+K/-K ratio), in fibroblasts from 15 normal controls was around 2.0 (1.8 to 2.4), whereas the +K/-K ratio in eight patients was always 1.0. The ratio for the 13 obligate carriers ranged from 1.4 to 1.9, causing a minor overlap with control. Identification of heterozygote cells by immunoblot analysis, using anti-T2 antibody alone as a probe, was difficult, as previously reported. We therefore carried out immunoblot analysis, using as probes a mixture of anti-T2 antibody and the antibody against mitochondrial 3-ketoacyl-CoA thiolase (T1), another mitochondrial thiolase, and determined the ratio of the intensities of the T2 and T1 bands (T2/T1 ratio) using a densitometer. When the T2/T1 ratio was calculated, there was no overlap between the heterozygotes and normal controls. Hence, the heterozygotes can be unambiguously identified using this method. The thiolase activities and T2/T1 proteins in immunoblotting were detectable in peripheral lymphocytes, rectal mucosa, amniocytes, and liver. Thus, the postnatal diagnosis of 3-ketothiolase deficiency can be readily made using lymphocytes or rectal mucosa. The applicability of these methods in amniocytes indicates that prenatal diagnosis of this disease should be possible.

Acetyl-CoA C-Acetyltransferase↗
PubMed1993

Comparison of the anticonflict effect of buspirone and its major metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) in rats.

The anxiolytic effects of buspirone and its major metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP) have been investigated with a conflict (shock-induced suppression of drinking) paradigm in rats. Buspirone (10 mg/kg, p.o.) showed an anticonflict activity with a bell-shaped dose-response relationship without any effect on spontaneous water consumption. Higher doses of buspirone reduced the punished response. Diazepam (20 and 40 mg/kg, p.o.) also showed an anticonflict activity in a dose-dependent manner, but animals with diazepam showed an increase in spontaneous water consumption at these doses. On the other hand, 1-PP (6.25-200 mg/kg, p.o.) showed a weak anticonflict activity with a significant effect at 25 mg/kg without any effect on spontaneous water consumption. In the 7-day treatment test, buspirone (5 and 10 mg/kg, p.o.), 1-PP (5 and 25 mg/kg, p.o.) and diazepam (10 and 40 mg/kg, p.o.) did not develop the tolerance to the anticonflict activity. Conversely, the anticonflict activity of diazepam was increased by the repeated treatment. Diazepam (10 mg/kg, p.o.) showed an anticonflict activity without any effect on spontaneous water consumption in this test. These results demonstrated that buspirone clearly exhibited an anticonflict effect similar to that of diazepam in a Vogel-type conflict test, and its real anxiolytic effect may not be always based on 1-PP, the main metabolite of buspirone.

Animals↗
PubMed1993

Isolation and characterization of Tn5-induced mutants of Pseudomonas paucimobilis UT26 defective in gamma-hexachlorocyclohexane dehydrochlorinase (LinA).

Pseudomonas paucimobilis UT26 grows on gamma-hexachlorocyclohexane (gamma-HCH) as a sole source of carbon and energy. Tn5 mutation was introduced into UT26, and two kinds of mutants defective in gamma-HCH degradation were phenotypically isolated; one (UT64) completely lacked the activity to degrade gamma-HCH, while the other (UT61) retained a very low level of activity. Tagging and sequencing analysis showed that both mutants had a Tn5 insertion at the same site of the linA (gamma-HCH dehydrochlorinase encoding) gene. However, UT61 had an additional rearrangement, which could be the cause of its retaining a low level of activity. An in vitro complementation test with a crude extract from UT64 plus partially purified LinA protein showed that LinA was essential not only for the first-step reaction (gamma-HCH to gamma-pentachloro-cyclohexene; gamma-PCCH), but also for the second-step reaction (gamma-PCCH to compound B) of gamma-HCH degradation in UT26.

Amino Acid Sequence↗
PubMed1993

A uterine muscle contractile substance obtained from a human placental cDNA library.

A cDNA clone coding for an oxytocin-like substance was prepared from a human placental cDNA library using oxytocin antiserum. The cDNA size was approximately 900 bp. A mammalian expression vector containing the cDNA was constructed and transfected into Chinese hamster ovary (CHO) cells. The expression of immunoreactivity to oxytocin antiserum was observed by radioimmunoassay. The cultured medium of the transfected cells was assayed for uterine muscle contractile bioactivity using a Magnus apparatus. Bioactivity was eliminated by incubation with oxytocin antiserum. Thus, the cDNA clone, screened with oxytocin antibody, is surmised to code for an oxytocin-like activity, but the nucleotide and amino acid sequences responsible for the biological activity remain to be clarified.

Animals↗
PubMed1993

A possible mechanism of inability of immunoglobulin heavy-chain production in Bence-Jones type myeloma cells.

To clarify the mechanism of the inability of immunoglobulin heavy (IgH) chain production in Bence-Jones (BJ) type myeloma cells, we examined the rearrangement of the IgH gene, the expression of IgH mRNA and the presence of functional nuclear factors that bind to the IgH gene enhancer in myeloma cells from 6 cases of BJ-type myelomas, and three myeloma cell lines and one Epstein-Barr virus-transformed B cell line having no IgH chain production. All BJ-type myeloma cells we examined showed rearranged bands by Southern blotting using the JH probe, and the rearrangement of VDJ segments in these cells was confirmed by PCR amplification of VDJ segments with consensus VH and JH primers. However, the expressions of IgH mRNA were not detected by Northern blotting in any of the BJ-type myeloma cells or the three non-producer myeloma cell lines. These findings suggested that the transcription of the IgH gene ceased in these cells, and alteration of this transcriptional apparatus may explain this inability. The functional nuclear factors that bind to IgH gene enhancers (HE2 and HE3) were absent in the myeloma cells from one case of BJ-type myelomas among these BJ-type myeloma cells and myeloma cell lines. This suggests that alteration of the enhancer binding factors may be one of the reasons why BJ-type myeloma cells are unable to produce the IgH chain.

Base Sequence↗
PubMed1993

[Tetralogy of Fallot with aortopulmonary window: report of a successful repair].

Tetralogy of Fallot is rarely associated with aortopulmonary window. A 6-month-old boy with tetralogy of Fallot, aortopulmonary window, pulmonary atresia, patent left superior vena cava and right aortic arch was operated successfully. Both great arteries were divided, the defect in the aortic wall was closed directly, and the defect in the pulmonary arterial wall was connected with a valved external conduit which was used for right ventricular outflow tract reconstruction. Although oliguria had been prolonged for 3 weeks post operatively, he recovered completely and RV/LV pressure ratio was less than 0.6 estimated by two-dimensional echocardiography at one month after operation.

Aortopulmonary Septal Defect↗
PubMed1993

[Anesthetic management of a patient with a history of right upper lobectomy for esophageal resection via left thoracotomy].

We anesthetized a patient for esophageal resection in a right lateral decubitus position, because of his right pleural adhesion after lobectomy for tuberculosis. Although hypoxemia was expected on left lung compression during the surgery, oxygenation was not compromised. A good ventilation/perfusion relationship might have been maintained in both the right and left lungs during the procedure.

Anesthesia, Epidural↗
PubMed1993

[A case report of aortic valve stenosis combined with complete A-V block during chronic hemodialysis].

A 52-year-old man treated by hemodialysis under the diagnosis of chronic renal failure admitted to our hospital due to aortic valve stenosis and complete A-V block. Aortic valve was severely calcified, and the cause of complete A-V block was considered caused by the progressive calcification invasing to conduction system. The aortic valve replacement and pacemaker implantation using myocardial lead were simultaneously. Postoperative course was uneventful. The efficacy of simultaneous operation of aortic valve and pacemaker implantation was emphasized. However the generator implantation was recommended to perform in the several days after the operation because of destruction of the pacemaker function by counter shock for arrhythmia in the early post operative period.

Aortic Valve Stenosis↗
PubMed1993

[Pseudoaneurysm of the left ventricle after mitral valve replacement: report of two cases without surgical repair].

We report two non-surgical cases of pseudoaneurysm of the left ventricle after mitral valve replacement. Two patients underwent uncomplicated mitral valve replacement with Ionescu-Shiley and Carpentier-Edwards bioprosthesis respectively, and both had good early postoperative course with no symptoms. Left ventriculogram one month after operation showed subvalvular pseudoaneurysm of the left ventricle in both patients. Two patients were in New York Heart Association Functional Class I with digitalis and diuretics and have left ventriculogram had done five years postoperatively. Pseudoaneurysm of the left ventricle without a surgical repair disappeared in one patient, and revealed no enlargement in the other. There still remain controversies regarding the treatment of pseudoaneurysm of the left ventricle following mitral valve replacement.

Aged↗