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Biomedical subjects

T Suzutani

Publications and source records attributed to T Suzutani.

At least 55 records · Page 3Linked to original sources

Different antiviral potencies of BV-araU and related nucleoside analogues against herpes simplex virus type 1 in human cell lines and Vero cells.

Antiviral potencies against herpes simplex virus type 1 (HSV-1) of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) and ten other nucleoside analogues in human embryonic lung fibroblast (HEL) cells were compared with those in Vero cells. 5-Halogenovinylarabinosyluracils, highly active in HEL cells, were inactive against all three laboratory-stocked strains of HSV-1 but exerted moderate antiviral effects on three clinical isolates in Vero cells. The reduction in anti-HSV-1 potencies of other representative nucleoside analogues in Vero cells was much less than those of 5-halogenovinylarabinosyluracils. However, significant antiviral potencies of BV-araU against laboratory strains were observed in other human and monkey fibroblast cells including an immortalized cell line. Significant enhancement of antiviral activity of BV-araU against a laboratory strain and a clinical isolate was demonstrated in Vero cells by the addition of 0.1 microM aminopterin or FUdR, an inhibitor of thymidylate synthesis. The potentiated anti-HSV-1 activity in Vero cells was comparable to the potency in HEL cells without the inhibitor. These results suggested that high activity of thymidylate synthesis and a large thymidylate pool size in Vero cells seem to be related to loss of anti-HSV-1 potency of BV-araU. Original tissue type, species, and the immortality may not be responsible for the reduced antiviral activity of BV-araU in Vero cells.

Aminopterin↗

Antiviral activity of oxetanocins against varicella-zoster virus.

Several new nucleosides with an oxetanosyl-N-glycoside group, named oxetanocins, were evaluated for their antiviral activities against varicella-zoster virus (VZV) in human embryo lung cells. 9-(2-deoxy-2-hydroxy-methyl-beta-D-erythro-oxetanosyl)guanine (OXT-G) and 9-(2-deoxy-2-hydroxymethyl-beta-D-erythro-oxetanosyl)-2- aminoadenine were effective against not only thymidine kinase-positive (TK+) VZV (YS strain) but also thymidine kinase-negative (TK-) VZV (YSR strain), whereas carbocyclic OXT-G was effective against TK+ VZV but not against TK- VZV. [3H]OXT-G was incorporated into TK+ VZV-infected cells and TK- VZV-infected cells more than into mock-infected cells and was converted into the triphosphate form.

Adenine↗

Effects of various nucleosides on antiviral activity and metabolism of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil against herpes simplex virus types 1 and 2.

Uptake of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) into herpes simplex virus type 1 (HSV-1)- and 2 (HSV-2)-infected cells was elevated about 190 to 40 times, compared with that into mock-infected human embryo lung fibroblast cells. Uptake was not enhanced by infection with thymidine kinase-negative HSV-1 and HSV-2 mutants, however. In HSV-1-infected cells, 9.7% of BV-araU was phosphorylated to BV-araU triphosphate, but only 1.1% was phosphorylated in HSV-2-infected cells. The antiviral effect, uptake, and turnover of BV-araU were inhibited significantly by thymidine (dThd), moderately by deoxyuridine, and not at all by deoxycytidine. On the other hand, the antiviral activity of acyclovir (ACV) was inhibited only by dThd. The effect of BV-araU was influenced by dThd and dThd phosphates (mono-, di-, and triphosphates), and the effect of ACV was influenced only by dThd, which competitively inhibited the phosphorylation of ACV to ACV monophosphate. The combination of 5-fluorodeoxyuridine (FUdR)-BV-araU or FUdR-ACV had a synergistic effect on HSV-1 and HSV-2 replication. The effect of FUdR on the turnover of BV-araU in HSV-1- and HSV-2-infected cells was analyzed by high-performance liquid chromatography. In HSV-1-infected cells, 86% of the BV-araU was phosphorylated to BV-araU triphosphate, but no effect was observed in HSV-2-infected cells, in which 98% of the BV-araU remained as BV-araU monophosphate.

Antiviral Agents↗

Efficacies of antiherpesvirus nucleosides against two strains of herpes simplex virus type 1 in Vero and human embryo lung fibroblast cells.

Antiviral activities of five nucleoside analogs against the VR-3 and WT-34 strains of herpes simplex virus type 1 (HSV-1) were investigated in Vero and human embryo lung fibroblast (HEL) cells. In HEL cells, the compounds showed antiviral activities against both strains of HSV-1, but in Vero cells, the antiviral activities of the compounds were reduced in proportion to their antiviral indexes (the 50% inhibitory dose [ID50] for cell growth divided by the 50% plaque reduction dose for virus). The ratio of the ID50 in Vero cells to the ID50 in HEL cells was larger in VR-3-infected cells than in WT-34-infected cells. The following results were obtained. (i) Thymidine kinase (TK; EC 2.7.1.21) activity in the VR-3- or WT-34-infected Vero cells was about half that in VR-3- or WT-34-infected HEL cells. Induction of viral TK was especially low in the VR-3-infected Vero cells. (ii) The ID50 of the plaque reduction assay in hypoxanthine, aminopterin, and thymidine medium revealed that the activity of cellular thymidylate synthetase (EC 2.1.1.45) was important in viral replication in VR-3-infected Vero cells. (iii) The VR-3-infected cells required larger thymidine and thymidine phosphate pools for viral replication than the WT-34-infected cells did, although uptake of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl) uracil into infected cells was equal for both strains. (iv) In the VR-3-infected Vero cells, the quantity of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil triphosphate was smaller than that in VR-3-infected HEL cells and WT-34-infected Vero and HEL cells.

Acyclovir↗

Study on the apparent resistant strains of herpes simplex virus type 1 against 9-beta-D-arabinofuranosyladenine.

The appearance of drug resistant strains of herpes simplex virus type 1 (HSV-1) against 9-beta-D-arabinofuranosyladenine (araA), in comparison with 5-iodo-2'-deoxyuridine (IUdR) and 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine, ACG), has been investigated in green monkey kidney cell cultures (Vero) and human embryo lung cell cultures (HEL). Growth curves of HSV-1 in Vero cells and HEL cells in the presence or absence of 20 micrograms/ml of araA showed that not only the viruses produced by these cells in the presence of araA but also the viruses produced in the absence of araA were resistant to the same concentration of araA. However, both viruses were unable to grow in the presence of a combination of 20 micrograms/ml of araA and 3 micrograms/ml of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) which is an inhibitor of adenosine deaminase. On the other hand, the viruses produced only in the presence of IUdR or ACG were resistant to each drug. All virus clones obtained from five serial clonings in the presence of araA alone or araA and EHNA in combination were not resistant to araA. These results show that the strain of HSV-1 resistant to araA is an apparently resistant strain, and a truly resistant strain to araA may not be established as easily as the truly resistant strains to IUdR and ACG.

Acyclovir↗

Correlation between augmented resistance to influenza virus infection and histological changes in lung of mice treated with trehalose-6,6'-dimycolate.

Mice inoculated intravenously with trehalose-6,6'-dimycolate (TDM), a glycolipid component of the cell wall of Mycobacterium, in an oil-in-water emulsion (TDM emulsion) acquired a high resistance to intranasal infection by influenza virus. Athymic nude mice inoculated with TDM emulsion could not acquire such an augmented resistance to influenza virus infection. The augmented antiviral resistance of TDM emulsion-treated mice was diminished by prior intravenous inoculation of silica particles, which selectively impair macrophage functions. In vitro experiments showed that macrophage cultures treated with TDM emulsion released an activator(s) of T lymphocytes. Histological studies of the lung of TDM emulsion-inoculated mice revealed that a typical granuloma and severe perivascular lymphocyte infiltration appeared, though no such histological change was observed in the lung of control emulsion-inoculated mice. The lungs from TDM emulsion-treated athymic nude mice and the lungs from silica particle- and TDM emulsion-treated mice showed fewer and smaller granulomata and milder perivascular lymphocyte infiltration than a typical granuloma and lymphocyte infiltration in the lungs of TDM emulsion-treated mice. These and earlier results suggest that an acquired antiviral resistance of TDM emulsion-treated mice was caused by elicitation of macrophages with TDM, then activation of T lymphocytes, leading to granuloma formation and an amplified earlier interferon production in response to influenza virus infection.

Animals↗

Role of interferon in the augmented resistance of trehalose-6,6'-dimycolate-treated mice to influenza virus infection.

Mice inoculated intravenously with 10 to 100 micrograms trehalose-6,6'-dimycolate in an oil-in-water emulsion (TDM emulsion) acquired high resistance to intranasal infection by influenza virus at 7 to 14 days, but not at 1 day, after treatment. Mice inoculated with an oil-in-water emulsion without TDM (control emulsion) did not resist infection. The activity of the reticuloendothelial system of mice inoculated with TDM emulsion or control emulsion was greatly stimulated 1 day and 14 days after treatment. Interferon production in response to influenza virus was augmented in lung and serum of TDM emulsion-treated mice. The augmented interferon production was greatly diminished in the TDM emulsion-treated mice by treatment with anti-Thy-1.2 monoclonal antibody. Production of haemagglutination-inhibiting antibody in the TDM emulsion-treated or control emulsion-treated mice was higher than that in untreated mice, although no difference was observed between the TDM emulsion-treated and control emulsion-treated mice. On the other hand, TDM emulsion treatment of mice did not influence the appearance of antibody-producing cells, nor the activity of natural killer cells in the mice. The enhanced resistance of mice was diminished by inoculating anti-interferon-alpha/beta serum before influenza virus infection. No detectable interferon activity was observed in lung and blood of mice inoculated with anti-interferon-alpha/beta serum prior to influenza virus infection. These results suggest that the augmented early interferon production in T-lymphocytes of TDM emulsion-treated mice in response to influenza virus may play an important role in the enhanced resistance.

Animals↗

Enhancement of interferon-gamma production in glycyrrhizin-treated human peripheral lymphocytes in response to concanavalin A and to surface antigen of hepatitis B virus.

The effects of glycyrrhizin, a component of licorice (Glycyrrhiza glabra) roots, on the production of interferon-gamma in human peripheral lymphocyte-macrophage cultures by concanavalin A (Con A) was examined. Interferon-gamma production in normal lymphocyte-macrophage cultures treated with 10 to 100 micrograms/ml of glycyrrhizin at 37 degrees C for 12 hr or longer, and then treated with 10 micrograms/ml of Con A, was enhanced four to eight times compared to control cell cultures. Lymphocyte-macrophage cultures treated with 10 to 100 micrograms/ml of glycyrrhizin alone did not produce interferon. No significant difference in the adsorption of [3H]Con A to glycyrrhizin-treated and control lymphocyte-macrophage cultures was found, but RNA and protein synthesis of the treated lymphocytes was increased compared to control cells; DNA synthesis, however, was reduced. Collaboration between enriched T-lymphocytes and macrophages, both treated with glycyrrhizin, was needed for the enhancement of interferon-gamma production. A smaller increase in interferon production was also observed in the glycyrrhizin-treated peripheral lymphocyte-macrophage cultures derived from an asymptomatic carrier of hepatitis B virus, in response to Con A and surface antigen of hepatitis B virus.

Cells, Cultured↗

[Investigations on ashing of animal tissues for the determinations of trace metals by means of polarography or atomic-absorption spectrometry (author's transl)].

A comparison has been made of three ashing methods for animal tissues with subsequent determination of minute quantities of metals by polarography or atomic-absorption spectrometry. Wet oxidation method with many disadvantages and few advantages has been shown not to be useful for the purpose. Both dry ashing in a muffle-furnace at 530 degrees C and low-temperature ashing are equally applicable to atomic-absorption spectrometry, but dry ashing in a furnace is more excellent with polarography. For obtaining ashes with constant compositions it is far more difficult with low-temperature ashing than with dry ashing in a furnace. Hence, dry ashing in a furnace is most widely applicable.

Animals↗

[Studies on the estimation of the postmortem interval. 9. Synthetic judgment of all sorts of cadaveric findings (author's transl)].

The authors have investigated the relationship between the postmortem interval and all sorts of cadaveric findings, summarizing the results of the previous reports, and have devised a cadaveric-phenomena diagram and a chart with which the postmortem interval can be estimated easily. The validity and utility of the diagram and the chart have been demonstrated by applying them to other autopsy cases than those from which they have been derived.

Adolescent↗

[Medico-legal studies on the deaths from coal-mine accidents. 1. Cadaveric phenomena (author's transl)].

The authors have investigated the cadaveric phenomena on 30 persons killed in coal-mine accidents being kept in pits for a long time after death. The conclusions are as follows: The appearance and progress of cadaveric phenomena in pits depend on the postmortem interval alone, not on the immediate causes of death which have been found to be of seven classes in coal-mine accidents. The phenomena on cadavers kept in pits are the same as those in the air of normal temperature on earth. The reason may be that there are both accelerative factors and suppressive factors among various environmental factors in pits after occurrence of accident and they offset each other to make no difference between cadavers in pits and those on earth.

Accidents, Occupational↗

[Studies on medico-legal diagnosis in cold district. 2. Cadaveric phenomena in low temperature surroundings (author's transl)].

The authors have investigated 14 kinds of findings of 15 cadavers in low temperature surroundings which had remained at known postmortem interval and had been subjected to medico-legal autopsies in our laboratory, comparing with those at normal temperature. In low temperature surroundings, the onset and progress of the findings due to autolysis or putrefaction are retarded in a marked degree but the turbidity of the cornea which is considered to be due to physical or chemico-physical phenomenon is retarded merely in a slight degree. Hence, an erroneous determination of the postmortem interval can be avoided by taking care of the peculiarity. Even the cadavers at low temperature display in 3 to 5 months after death the findings whose degrees correspond to those of the cadavers at normal temperature in 4 to 7 days after death. Some fly-larvae pass the winter on cadavers demonstrating that the time of death was towards the end of autumn of the preceding year.

Adolescent↗

[Studies on medico-legal diagnosis in cold district. 3. Autopsy findings of the victims of cold exposure (author's transl)].

The authors have investigated the autopsy findings of 8 bodies died from cold. The conclusions are as follows: Pink colour of the blood in the left ventricle or the pulmonary veins, pink colour of the lungs and pink patches of the skin are fairly pathognomic findings of death from cold. Seven out of eight bodies have presented at least one of these findings. Subserous or submucous hemorrhage is less pathognomic and has been presented less frequently.

Adult↗

[Studies on medico-legal diagnosis in cold district. 4. An experimental study on the rise of temperature of dead body caused by the radiation of sunlight (author's transl)].

A sausage of 4 cm diameter and 15 cm length was chosen as a model of a part of human extremities. On the snowfield the model was stood on end and its temperature was recorded continuously by means of thermistor thermorecorder. The conclusions are as follows: In fine weather the temperature directly under the sunny surface of a model rose higher than the air temperature by 18 degrees C in the most remarkable case. Even in cloudy weather it rose fairly though lower than in fine weather. The rise of a model temperature became higher in February than in January. Even at a depth of 1.0 cm the temperature rose fairly though lower than directly under the surface. The temperature of the shady side of a model was equal to air temperature or snow temperature. It is presumed from these data that the temperature of a human dead body on snowfield becomes higher and reaches a optimum temperature for putrefaction at least partly by the radiation of sunlight. The presumption is supported by our experiences at the autopsies in cold district.

Autolysis↗

[Studies on medico-legal diagnosis in cold district. 5. The blood shed on the snow (author's transl)].

By using bovine blood as a model, the authors have observed the forms and patterns of the blood drops shed or spurted on the snow and the extent of a large amount of blood absorbed in the deep snows, investigating the influence of the properties of snow upon them. It has been demonstrated that the polarographic method is most excellent for the purpose of determining the amount of blood absorbed in the snow.

Animals↗

[Medico-legal studies on the deaths from coal-mine accidents. 2. Exogenous findings (author's transl)].

Thirty-four deceased who were killed from twenty cases of coal-mine accidents during fourteen years from 1965 to 1978 were autopsied in our laboratory and the following conclusions have been obtained, summarizing the exogenous findings on the bodies. At the explosion of methane gas and coal dust chemical energy stored in coal or methane is converted to mechanical energy and thermal energy which act upon the human bodies. Mechanical energy produces diverse injuries in the human bodies, among which only the coal-particle impression demonstrates directionality. Thermal energy produces burns when it acts directly upon the human bodies and among diverse substances produced by heat from the explosion coal-tar like substance adheres to the skin, soot adheres to the inside of the air passage, carbon monoxide produces carbon-monoxide hemoglobin after entering the blood through the lung. At gas spurt mechanical energy stored in methane which is adsorbed on coal under high pressure is set free to produce injuries on the human bodies, but thermal energy does not develop. The action of diverse sorts of energy upon the body differs extraordinarily according to the distance from an epicenter or the irregularities of pit, producing various exogenous findings on the bodies. Accordingly, general rules cannot be established to assume the sort and mode of an accident and it should be considered on a case-by-case basis.

Accidents, Occupational↗

[Medico-legal studies on the deaths from coal-mine accidents. 3. Causes of death (author's transl)].

Thirty-four deceased who were killed from twenty cases of coal-mine accidents during fourteen years from 1965 to 1978 were autopsied in our laboratory and their causes of death have been discussed. In the explosion of methane gas and coal dust chemical energy stored in coal or methane is converted to mechanical energy and thermal energy which act upon the human bodies to bring about seven sorts of causes of death. Deaths are caused more frequently by thermal energy directly or indirectly than by mechanical energy. It is a characteristic found in the explosions of coal mines which are large and closed underground spaces consisting of inflammable material. In gas spurt major cause of death is asphyxia from the lack of oxygen resulting from the substitution of air by methane gas and the effects of mechanical energy developed by gas spurt is slight in degree. In the coal-mine accidents the causes of death are so much concurred that is is difficult to certify the cause of death. A new concept of a cause of death has been proposed to solve such a problem.

Accidents, Occupational↗