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Biomedical subjects

A Seto

Publications and source records attributed to A Seto.

At least 37 records · Page 2Linked to original sources

Effect of dietary seal and fish oils on triacylglycerol metabolism in rats.

Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were distributed mainly in the sn-1 and 3 positions of seal oil triacylglycerol and in the sn-2 position of fish oil triacylglycerol. Seal oil or fish oil-rich fats having constant polyunsaturated/monounsaturated/saturated fatty acids and n-6/n-3 polyunsaturated fatty acid (PUFA) ratios were fed to rats for 3 wk. Control rats were fed on a fat containing linoleic acid as the sole PUFA. Seal oil more effectively lowered serum and liver triacylglycerol concentrations than fish oil. The activities of fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH) and hepatic triacylglycerol lipase (HTGL) were significantly lower in the seal oil group than in the control group, whereas the activity of HTGL was significantly lower and the hepatic peroxisomal beta-oxidation and activity of lipoprotein lipase (LPL) in adipose tissue were significantly higher in the fish oil group than in the control group. These observations suggest that the predominant hypotriacylglycerolemic effect of seal oil is caused by the suppression of fatty acid synthesis.

Adipose Tissue↗

[Anesthetic management of a patient with Bartter's syndrome].

A 48-year-old woman with Bartter's syndrome underwent right mastectomy under general anesthesia. Her operative course was uneventful. She was preoperatively complicated with severe hypokalemia but had no signs and symptoms of hypokalemia. In anesthetic care of patients with Bartter's syndrome, even when they have no symptoms of hypokalemia, the meticulous intravenous administration of potassium chloride is required in order to maintain the preoperative level of the serum potassium during anesthesia. In addition, attention should be paid to factors causing an additional reduction in the serum potassium concentration, such as alkalosis, elevated beta 2-adrenergic activity, increased availability of insulin and hypothermia.

Anesthesia, General↗

A primitive pathway of porphyrin biosynthesis and enzymology in Desulfovibrio vulgaris.

Culture of Desulfovibrio vulgaris in a medium supplemented with 5-aminolevulinic acid and L-methionine-methyl-d3 resulted in the formation of porphyrins (sirohydrochlorin, coproporphyrin III, and protoporphyrin IX) in which the methyl groups at the C-2 and C-7 positions were deuterated. A previously unknown hexacarboxylic acid was also isolated, and its structure was determined to be 12, 18-didecarboxysirohydrochlorin by mass spectrometry and 1H NMR. These results indicate a primitive pathway of heme biosynthesis in D. vulgaris consisting of the following enzymatic steps: (i) methylation of the C-2 and C-7 positions of uroporphyrinogen III to form precorrin-2 (dihydrosirohydrochlorin); (ii) decarboxylation of acetate groups at the C-12 and C-18 positions of precorrin-2 to form 12,18-didecarboxyprecorrin-2; (iii) elimination of acetate groups of the C-2 and C-7 positions of 12,18-didecarboxyprecorrin-2 to form coproporphyrinogen III; and (iv) conversion of coproporphyrinogen III to protoporphyrin IX via protoporphyrinogen IX. We isolated the following three enzymatic activities involved in steps i-iii from the soluble fraction of the cells by anion-exchange chromatography: S-adenosyl-L-methionine:uroporphyrinogen III methyltransferase, precorrin-2 12,18-acetate decarboxylase, and 12, 18-didecarboxyprecorrin-2 2,7-decarboxymethylase; all enzymic products were converted into autooxidized methyl esters and analyzed by thin-layer chromatography, UV-visible (UV-VIS) absorption, and mass spectrometry. The enzymatic reactions in D. vulgaris shed new light on porphyrin biosynthesis at an early stage in the evolution of prokaryotes.

Chromatography, Thin Layer↗

Effects of long-term feeding of marine oils with different positional distribution of eicosapentaenoic and docosahexaenoic acids on lipid metabolism, eicosanoid production, and platelet aggregation in hypercholesterolemic rats.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were distributed mainly in the sn-1,3 positions of seal oil triglyceride and in the sn-2 position of squid oil triglyceride. Seal oil-rich or squid oil-rich fats having constant saturated/monounsaturated/polyunsaturated fatty acid (PUFA) and n-6/n-3 PUFA ratios were fed to exogenously hypercholesterolemic rats for 1 60 d. The control fat contained linoleic acid as the sole PUFA. Before starting the experimental diets, rats were orally treated with high doses of vitamin D for 4 d to accelerate atherogenesis. The percentage of arachidonic acid in phosphatidylcholine and phosphatidylethanolamine of liver, platelets, and aorta was lower in the marine oil groups than in the control group, seal oil being more effective than squid oil. Maximal platelet aggregation induced by collagen was significantly lower in both marine oil groups. Platelet thromboxane (TX) A2 production induced by collagen or thrombin was markedly reduced by feeding seal or squid oils, the reduction being more pronounced in the seal oil than in the squid oil group. Aortic prostacyclin (PGI2) production was the same among the three groups. The ratio of the productions of aortic PGI2 and platelet TXA2 was significantly higher in the seal oil than in the control group. Although there was no difference in intimal thickness among the three groups, the aortic cholesterol content was significantly lower in the marine oil groups than in the control group. These results showed that the main effects in rats of the different intramolecular distributions of EPA and DHA in dietary fats were on arachidonic acid content in tissue phospholipids and on platelet TXA2 production.

Animals↗

Antitumor killer lymphocytes in the peripheral blood of a patient with transitional cell carcinoma of the bladder.

BACKGROUND: Peripheral blood lymphocytes (PBL) from patients with bladder cancer also contain cells possessing cytotoxic activity against autologous tumor cells. These cells are phenotypically heterogenous and include natural killer (NK) and cytotoxic T cells. This study investigated the role of cytotoxic lymphocytes directed against autologous bladder cancer cells. METHODS: PBL were obtained at intervals before and after surgery and analyzed for cytotoxic activity against autologous bladder cancer cells in 4-hour 51Cr release assay. PBL stimulated with autologous tumor cells were also transformed with human T-lymphotropic virus type-1, establishing a cell line (KB31) which was analyzed for phenotype and cytotoxic activity against the autologous tumor cells. RESULTS: PBL preoperative cytotoxic activity was low, but increased after surgery. Cytotoxic activity was found not only against autologous bladder cancer cells, but also against heterologous bladder cancer (KK-47) and myeloid leukemia (K562) cells, with the highest activity against the heterologous cell lines. The cytotoxic activity of KB31 was 40% against autologous tumor cells 6 weeks after initiation of the cell line, but decreased to 5% by 6 months. This activity was lower than that against the other cell lines, and was similar to that of PBL in short-term culture. Fluorescence-activated cell sorter (FACS) analysis demonstrated that in KB31 cells at 6 weeks, CD8+ cells were dominant, but CD56+ cells predominated at 6 months. CONCLUSION: These results suggest that the presence of cytotoxic activity in the peripheral blood of the patient was due to both cytotoxic T cells and NK cells. The cytotoxic activity was lowest prior to surgery and increased postoperatively.

Aged↗

Pregnancy outcome following first trimester exposure to antihistamines: meta-analysis.

To determine the relative risk for major malformations associated with antihistamine (H1 blockers) exposure in the first trimester of pregnancy, a literature search of all studies examining the association between antihistamines and major malformations for the period 1960 to 1991 was conducted, followed by meta-analysis. Odds ratio was calculated using the Mantel-Haenszel method. Twenty-four controlled studies met the inclusion criteria with more than 200,000 participating women. The summary odds ratio of major malformations associated with antihistamines taken during the first trimester was 0.76 (95% CI: 0.60-0.94). This analysis indicates that H1 blockers used mainly for morning sickness during the first trimester do not increase the teratogenic risk in humans and may, in fact, be associated with a protective effect. More study is needed to verify the possibility that by preventing vomiting, antihistamines may ensure better metabolic conditions to the fetus and thus may reduce some birth defects. Alternatively, it is possible that pregnancies characterized by vomiting are associated with better outcome due to other reasons, such as hormonal status or placental function. Women suffering from morning sickness which is not controlled by nonpharmacological methods can safely use antihistamines.

Abnormalities, Drug-Induced↗

Alteration of E-cadherin and alpha N-catenin immunoreactivity in the mouse spinal cord following peripheral axotomy.

We examined the effects of peripheral axotomy on the immunoreactivity of E-cadherin and cadherin-associated protein alpha N-catenin in the spinal cord. E-cadherin is known to be exclusively expressed in lamina II of Rexed in the spinal cord dorsal horn. This expression disappeared by day 7 after axotomy and reappeared following nerve ligature (partial axonal regeneration model) on day 63. In contrast, it remained undetectable following nerve clipping (complete degeneration model). Alpha N-catenin was diffusely stained in the gray matter, and the immunoreactivity was specifically intense in the central canal and superficial dorsal horn. The expression of alpha N-catenin in the superficial dorsal horn was similarly reduced by day 7 after axotomy, but recovered by day 63 after nerve ligature. In contrast, it remained at the reduced level after nerve clipping. The alteration of alpha N-catenin immunoreactivity showed a similar pattern consistent with that of E-cadherin. Administration of nerve growth factor (NGF) rescued the immunoreactivity of substance P, which is known to disappear after peripheral axotomy, but not influence that of both E-cadherin or alpha N-catenin. These results clearly showed that peripheral axotomy simultaneously alters the immunoreactivity of E-cadherin and alpha N-catenin in the spinal cord, suggesting a correlation in the expression of both E-cadherin and alpha N-catenin in vivo. E-cadherin-alpha N-catenin complex might be crucial for plasticity of the spinal cord dorsal horn after peripheral axotomy.

Animals↗

Resistance to herpes simplex virus type 1 and its latent infection of human T cell lymphotropic virus type I-transformed T cell lines of rabbits.

Fourteen T cell lines of rabbits were infected with herpes simplex virus type 1 (HSV-1) and examined for their susceptibility to lytic infection and ability to support virus replication. T cell lines of CD4+ 8- phenotype were more vulnerable to lysis and supported higher levels of virus replication than those of other phenotypes. Cell lines of CD4+ 8+ and CD4- 8+ phenotypes continued to proliferate, while remaining productively infected, for more than a month. These latently infected cell lines could be established by treatment with anti-HSV-1 serum and complement. Viral genes were only partially expressed and the CD8 membrane antigen was down-regulated. Infected cell lines, as well as peripheral blood lymphocytes, were shown to induce meningoencephalitis when inoculated intravenously into syngeneic hosts, suggesting a possible role for infected lymphocytes in HSV-1 transport in vivo.

Animals↗

Induction of apoptosis in human leukemic cells by magnetic fields.

When human myelogenous leukemic cell lines, HL-60 and ML-1, were exposed to 50 Hz electromagnetic fields (EMFs), nucleosome-sized DNA fragmentation (a biochemical marker of apoptosis) was induced as assessed by agarose gel electrophoresis. However, EMFs could not induce detectable DNA fragmentation in either human peripheral blood leukocytes or polymorphonuclear cells. The minimum exposure period required for the onset of DNA fragmentation in leukemic cells was 1.0 h. Although adverse effects of EMFs on human health have been reported, the apoptosis-inducing action of EMFs on leukemic cells may suggest a possible medical application.

Apoptosis↗

Glucosylceramide synthetase inhibitor, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol exhibits a novel decarcinogenic activity against Shope carcinoma cells.

The glucosylceramide synthetase inhibitor, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) was tested to determine whether it could exhibit anti-tumor activity against two different Shope carcinoma cell lines. The cell growth was suppressed in a dose-dependent manner in the presence of D-PDMP. This supression seem to be accounted for by prolongation of the lag phase and this phenomenon was especially marked in the undifferentiated cell line. The growth suppression was also partly explained by direct inhibition of cell proliferation because the suppression was released by removing the agent from the medium. The treated cells became morphologically differentiated with lower density at confluence and regained contact inhibition in flask culture. Colony-forming ability in soft agar, which has been reported to be closely correlated with tumorigenicity, was also inhibited dose-dependently in the presence of D-PDMP. These results suggested that D-PDMP could exhibit a novel decarcinogenic activity against Shope carcinoma cells.

Animals↗

Analysis of T cell receptor V beta expression in rabbit T lymphocytes induced to proliferate by an HTLV-I-transformed leukemogenic T cell line.

Peripheral blood lymphocytes (PBL) from rabbits of the Chbb:HM strain proliferated in coculture with an X-ray-irradiated HTLV-I-transformed leukemogenic cell line of (B/J x Chbb:HM) F1 origin, whereas PBL from rabbits of the B/J and F1 strains hardly proliferated at all in co-culture with the same cell line. A proviral HTLV-I genome was detected in high-molecular-mass DNA from these proliferating cells. An analysis of T cell receptor V beta expression revealed that these lymphocytes were of restricted V beta subfamilies, suggesting that the preferential stimulation and transformation of lymphocytes occurred in this co-culture. Staphylococcal enterotoxins similarly stimulated lymphocytes and the proliferated lymphocytes were mostly of distinct V beta subfamilies depending on stimulator enterotoxins. These results suggested that the leukemogenic cell line possesses an antigen that preferentially stimulates lymphocytes of restricted V beta subfamilies.

Animals↗

Cloning and characterization of a new allergen, Mag 3, from the house dust mite, Dermatophagoides farinae: cross-reactivity with high-molecular-weight allergen.

A new immunoreactive clone whose sequence is not homologous to that of any of the previously identified mite allergens was isolated by successive immunoscreening of a Dermatophagoides farinae cDNA library with rabbit antisera to an extract of the house dust mite and IgE in pooled sera from patients allergic to mites. Rabbit antibodies specific for the recombinant protein recognized a 177 kD protein in a mite body extract. This immunoreactive protein was located in the circumferential tissues of esophagus, gut and the other internal organs in mites. The reaction of human IgE to the purified natural antigen was inhibited competitively to 30% by the recombinant antigen. In terms of the frequency and the intensity of response to specific IgE in sera from asthmatic patients, the natural protein was similar to Der f2, while the recombinant protein was slightly less allergenic by these criteria. We conclude that the natural protein from the house dust mite, D. farinae, is an important allergen.

Amino Acid Sequence↗

Localization of E-cadherin in peripheral glia after nerve injury and repair.

Peripheral nerve injury results in histological and histochemical changes in neurons and glia. We have recently found that Ca(2+)-dependent cell adhesion molecule E-cadherin plays an important role in the selective fasciculation of a particular subset of unmyelinated sensory fibers. In the present immunohistochemical and immunoblot analyses, the temporal profile of the subcellular expression of this molecule in spinal nerves was examined after crushing, transecting, or ligaturing the sciatic nerve in mice with special attention paid to E-cadherin expression in glial cells. After axotomy of the sciatic nerve, distal axons of the proximal stump and the fibers of the distal stump degenerated, but E-cadherin was still detectable at the outer mesaxons of the myelinated axons as long as they remained morphologically intact. Subsequently, Schwann cells proliferated and migrated to form Schwann cell columns (Büngner's bands) as initial responses to denervation, and expressed E-cadherin at their site of contact with each other and later with sprouting axons. At the initial stage of myelin formation, slender processes of a single Schwann cell interdigitated with an enveloped axons, and expressed E-cadherin at the contact site elaborated by a single Schwann cell. Immunoblot analysis on day 7 revealed that E-cadherin was detected in both the proximal nerve segments and the regenerative distal segments, but was negative in the degenerative distal segments. On the basis of present data, it is suggested that E-cadherin might be involved in the stabilization of the peripheral glial network which provides the guidance of sprouting axons and myelination.

Animals↗

Lymphatic absorption of seal and fish oils and their effect on lipid metabolism and eicosanoid production in rats.

Eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) were distributed mainly in the sn-1 and 3 positions of seal oil triglyceride and in the sn-2 position of fish oil triglyceride. In Expt. 1, the structural distribution of EPA and DHA in lymph triglyceride of rats given seal or fish oils was similar to the distribution in the administered oils. In Expt. 2, seal oil-rich or fish oil-rich fats having constant polyunsaturated/monounsaturated/saturated fatty acids and n-6/n-3 polyunsaturated fatty acids ratios were fed to rats for 3 weeks. Seal oil more effectively reduced plasma and liver triglyceride than fish oil. Ratio of the productions of aortic prostacyclin and platelet thromboxane A2 stimulated by thrombin was significantly higher in rats fed seal oil than in those fed fish oil. The results suggested that the different intramolecular distribution of EPA and DHA in dietary fat affected lipid metabolism differently in rats.

Absorption↗

Expression of NF2 gene product merlin in arachnoid villi and meningiomas.

Neurofibromatosis type 2 (NF2) gene encodes a novel 595 amino acid protein named merlin. Recently, Ruttledge et al demonstrated inactivation of NF2 gene in approximately 60% of sporadically occurring meningiomas. Merlin is thought to physiologically exist beneath the cell membrane, and to form a part of modulation in signal transduction, for example, information concerning contact inhibition. In NF2-related tumors, it is supposed that the mutation of merlin results in loss of this signal transduction leading to tumorigenesis. In this paper, we investigated the expression of NF2 gene product merlin in arachnoid villi and meningiomas. The immunohistochemical staining of merlin showed a striking contrast between arachnoid villi and meningiomas. In arachnoid cells, merlin was labeled in the whole cytoplasm, but not within the nuclei. In contrast, in meningiomas, immunoreactivity of merlin was mainly seen in the nuclei. These results suggest that arachnoid cells with normal merlin are capable of normal signal transduction, whereas meningioma cells with mutated merlin show impairment of signal transduction which may lead to tumorigenesis.

Arachnoid↗

Variable-region sequences for T-cell receptor-gamma and -delta chains of rabbit killer cell lines against Shope carcinoma cells.

A rabbit gamma delta killer T-cell line against Shope carcinoma cells was established from peripheral blood lymphocytes (PBL) of a human T-lymphotropic virus type I (HTLV-I)-infected rabbit bearing Shope papilloma and carcinoma. Southern hybridization analysis of this cell line with an HTLV-I probe showed that the cell line contained multiple clones of HTLV-I-transformed cells, and three sublines with different integration patterns of the HTLV-1 genome were isolated by cloning of the cell line. In all these sublines T-cell receptor (TCR)-gamma and -delta genes were rearranged and expressed. A PCR-based analysis of the expression of variable (V) genes showed that the killer cell line preferentially expressed V gamma 1.1 and V delta 1 genes, whereas V gamma 2 and V delta 1 genes were dominantly expressed in normal PBL. Analysis of the junctional sequences of TCR-gamma and -delta genes which dictate the fine specificities of epitope recognition revealed that all three sublines expressed V gamma 1.1/V delta 1 genes without the nucleotide diversity at the V-J junctions.

Amino Acid Sequence↗

Genetic susceptibility to herpetic encephalitis of inbred rabbits of B/Jas strain.

Inbred rabbits of B/Jas strain were found to be highly susceptible to herpes simplex virus type 1 encephalitis, following i.v. injection of the virus, while Chbb:HM strain rabbits were not susceptible. The susceptibility trait seemed to be inherited recessively, involving multiple genes, because (B/Jas x Chbb:HM)F1 hybrids were as resistant as Chbb:HM rabbits, and because more than 90% of backcrosses of (B/Jas x Chbb:HM)F1 to B/Jas were resistant to viral inoculation. The encephalitis in B/Jas rabbits resembled human herpes simplex encephalitis, in that the temporal lobe as well as the brain stem were affected preferentially, leading to the development of various types of seizures, such as circling, loss of balance leading to a fall, and tonic and clonic convulsions. The disease could be diagnosed by magnetic resonance imaging (MRI) analysis before onset of seizures, and diseased rabbits showed a marked lymphopenia at onset of seizures.

Animals↗