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Biomedical subjects

H Machida

Publications and source records attributed to H Machida.

At least 127 records · Page 7Linked to original sources
PubMed1983

Oxidation of acetylpolyamines by extracellular polyamine oxidase produced by Penicillium sp. No. PO-1.

The oxidation of acetylpolyamines by an extracellular polyamine oxidase of Penicillium sp. No. PO-1 was investigated. The optimal pH value for oxidation of acetylpolyamines was 6.0. The purified enzyme oxidized spermidine, spermine, N1-acetylspermidine, N8-acetylspermidine, N1,8-diacetylspermidine, N1-acetylspermine and N1,12-diacetylspermine. The relative velocities for oxidation of acetylpolyamines were lower than those of spermidine and spermine. The Km values for oxidation of acetylpolyamines were higher than those of spermidine and spermine. The enzyme split N1-acetylspermidine and N8-acetylspermidine at the same position of the linkage as in spermidine oxidation. N1-Acetylspermine was changed to N1-acetylspermidine. This oxidation mechanism was different from that of rat liver polyamine oxidase. N1-Acetylspermine inhibited the oxidation of spermine. Putrescine, N8-acetylspermidine and N1,12-diacetylspermine also inhibited the N1-acetylspermidine oxidation by the enzyme.

Animals↗
PubMed1982

Comparison of the in vitro and in vivo anti-herpes activities of 1-beta-D-arabinofuranosylthymine and its 5'-monophosphate.

In vitro and in vivo anti-herpes activities of 1-beta-D-arabinofuranosylthymine 5'-monophosphate (ara-TMP) were compared with those of 1-beta-D-arabinofuranosylthymine (ara-T). On a molar basis ara-TMP was almost as active as ara-T against six strains of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) as monitored by a cytopathogenicity-inhibition and a plaque reduction assay in human embryonic lung fibroblast cells. When tested against experimental encephalitis in mice inoculated intracerebrally with HSV-1, intraperitoneal or intravenous treatment with 150 mg/kg/day of ara-TMP or 100 mg/kg/day of ara-T, for 5 days was effective in increasing in the mean survival time of mice. For a single dose of ara-TMP, intravenous administration was more effective than intraperitoneal or oral administration. However, oral administration of ara-T was the most effective of the treatment regimens used. Substantial plasma levels of ara-T were detected for a longer time after oral administration of ara-T than after intravenous administration of ara-TMP or ara-T, suggesting that the efficacy of oral administration of ara-T may be correlated with the maintenance of the substantial blood drug levels.

Animals↗
PubMed1982

Phase I-II trials of poly(ICLC) in malignant brain tumor patients.

Poly(ICLC) preparation, containing poly-L-lysine and poly(I) . poly(C) at a weight ratio of 1:2, was given intravenously at a dose of 0.05 to 0.2 mg/kg to 7 patients with malignant brain tumor. Poly(ICLC) induced significant serum interferon (more than 100 reference units/ml) in all patients. The highest interferon titer induced was 875 reference units/ml. Severe side effect was not observed except fever. Hypotension, leukopenia and elevation of liver enzyme levels were observed as side effects in a few cases.

Adult↗
PubMed1982

Inhibitory effects of antiherpesviral thymidine analogs against varicella-zoster virus.

Thymidine analogs highly active against herpes simplex virus were compared in their inhibitory action against seven strains of varicella-zoster virus by a plaque reduction assay. E-5-Bromovinyl-arabinosyluracil (BV-ara-U) was most active, followed by E-5 chlorovinyl-arabinosyluracil, E-5-bromovinyl-2'-deoxyuridine (BV-dUrd), 2'-fluoro-5-methyl-arabinosyluracil, 2'-fluoro-5-iodo-arabinosylcytosine, arabinosylthymine, 5-vinyl-arabinosyluracil, acycloguanosine, and 5-iodo-2'-deoxyuridine, in order to decreasing activity. BV-ara-U was more than 10 times as active as BV-dUrd and almost completely inhibited plaque development of five strains of varicella-zoster virus at a concentration as low as 1 ng/ml.

Antiviral Agents↗
PubMed1982

[Effect of interferon inducer (poly ICLC) in the treatment of malignant brain tumor (author's transl)].

Interferon inducing activity, antitumor activity and toxicity of poly ICLC (poly IC stabilized with poly L-Lysine and carboxymethyl cellulose) in rodents were studied. SD strain rats were injected intravenously with poly IC or poly ICLC. Interferon in rat plasma was assayed by a plaque reduction method using stomatitis virus. The peak level of plasma interferon of the poly ICLC injection rat was as high as that of poly IC injection rat, and in the former, high level of plasma interferon persisted for 4-12 hours. Next, brain tumor-bearing rats were treated intravenously with poly ICLC and observed for death daily. Weekly treatment with 1 mg/kg of poly ICLC increased the mean survival time although no antitumor effect was observed with poly IC. The LD 50 value of poly IC was 33.5 mg/kg, and that of poly ICLC was 18.6 mg/kg and as to poly ICLC administration, no remarkable side effect was recognized below the dose of 1.5 mg/kg. In clinical trials, poly ICLC was given intravenously at the dose of 0.05-0.2 mg/kg to 9 patients with malignant brain tumor. (6 patients were glioblastoma, 1 was astrocytoma, and 2 were ependymoma.) In 2 patients, poly ICLC was administered once, in 2 patients twice, in 2 patients 3 times, and in 3 patients more than 5 times. The interval of each administration was 7 days. Poly ICLC induced high level of serum interferon (more than 100 reference unit/ml) in all patients and over 100 unit/ml of interferon was maintained for 24 hours. The highest interferon titer induced was 875 unit/ml. The most frequently encountered toxic reaction was fever, which occurred in all cases. The mean peak temperature elevation was 1.9 degrees C, which usually occurred 4-8 hours after drug administration. Modest hypotention was detected in one case. Leucopenia was detected in 3 cases. These abnormalities were all modest, and improved in a few days. As to the effect of poly ICLC, neurological improvement was recognized in 3 cases, and in one of them, remission on CT scan was also recognized.

Adult↗
PubMed1981

Antiherpesviral and anticellular effects of 1-beta-D-arabinofuranosyl-E-5-(2-halogenovinyl) uracils.

1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl) uracil (BV-ara-U) and 1-beta-D-arabinofuranosyl-E-5-(2-chlorovinyl)uracil (CV-ara-U) were tested for their anti-herpesviral activity in virus rating method, a plaque reduction method, and a virus yield reduction method, using human embryonic lung fibroblast (HEL-F) cells, At a concentration as low as 0.1 microgram/ml, both drugs exerted a marked inhibitory effect on the development of cytopathogenic effect induced by herpes simplex virus type 1 (HSV-1) infection and on the multiplication and plaque formation of HSV-1. Neither BV-ara-U nor CV-ara-U was significantly active against HSV type 2 (HSV-2). They scarcely inhibited growth of HEL-F cells, mouse L, and murine leukemia cells. Compared with 1-beta-D-arabinofuranosylthymine and 5-iodo-deoxyuridine, BV-ara-U and CV-ara-U were more than 10 times as active against HSV-1 and much less active against HSV-2. BV-ara-U was as active as E-5-(2-bromovinyl)-2'-deoxyuridine against HSV-1 and less inhibitory to growth of HEL-F cells. Cellular deoxyribonucleic acid synthesis was not significantly influenced by the new derivatives of arabinosyluracil, even at a concentration as high as 300 microgram/ml. The derivatives showed extremely marked inhibition of deoxyribonucleic acid synthesis in HSV-1-infected cells, whereas their inhibitory effect on deoxyribonucleic acid synthesis in HSV-2-infected cells was much lower than that in HSV-1-infected cells. These findings indicate that BV-ara-U and CV-ara-U are selectively inhibitory to HSV-1 multiplication.

Antiviral Agents↗
PubMed1981

Differential activity of potential antiviral nucleoside analogs on herpes simplex virus-induced and human cellular thymidine kinases.

Potential antiviral nucleoside analogs 1-beta-D-arabinofuranosylthymine, the 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-nucleosides of -5-methyluracil, -5-iodouracil, -5-methylcytosine, -5-iodocytosine, and -E-5-(2-bromovinyl)uracil, E-5-(2-bromovinyl)-2'-deoxyuridine, E-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil, and 9-(2-hydroxyethyoxymethyl)guanine were studied to compare their phosphorylation rates relative to thymidine by purified thymidine kinases from human and herpes simplex virus sources. Most of these analogs are capable of being phosphorylated by both human and viral enzymes. On the assumption that inhibition constants (Ki) reflect binding affinity, Ki values were determined for these analogs with the same thymidine kinases. In general, these analogs have a greater affinity for the viral enzymes. The amount of the analogs phosphorylated to the monophosphate form, which is presumably necessary to produce cytotoxic effects, was determined by the combined effects of phosphorylation rates and binding affinities. All of these analogs act as preferential substrates for the viral thymidine kinases at low concentrations, which may be one of the main reasons for their selective antiviral action.

Antiviral Agents↗
PubMed1981

Influence of progesterone on arterial blood and CSF acid-base balance in women.

To study the mechanism of the action of progesterone on pulmonary ventilation during pregnancy, arterial and cerebrospinal fluid (CSF) acid-base parameters were measured in 59 pregnant and 36 nonpregnant women at the periods of follicular phase, luteal phase, early pregnancy, late pregnancy, and puerperium. Marked respiratory alkalosis in both arterial blood and CSF was observed in pregnancy and puerperium. The degree of hypocapnia observed in the luteal phase and during pregnancy was closely related to the progesterone level in arterial blood. In conclusion, it is unlikely that the observed hyperventilation results from stimulation at the central chemosensitive areas or peripheral chemoreceptors.

Acid-Base Equilibrium↗
PubMed1981

[Roentgenological measurement of the cervical vertebral bodies in ossification of the posterior longitudinal ligament (OPLL) and cervical spondylosis (CS) (author's transl)].

Many studies of the pathogenesis of ossification of posterior longitudinal ligaments (OPLL) have been reported, and both general and local factors have been pointed out. In case a longitudinal ligament is affected by both the general and local OPLL factors for many years, the shape and size of the cervical vertebral bodies and the arrangement of the cervical spinal column might be affected. The relation between OPLL and disc degeneration, the morphology of the facet joint and the change of longitudinal ligament tension has been reported by many authors. But the relation between OPLL and the shape, size and arrangement of cervical vertebral bodies has not been reported. We selected X-ray films of the lateral view of cervical spines which had been taken at our hospital since 1975. The subjects consisted of 190 cases in Group I and 189 cases in Group II. Half of Group I had OPLL, of which 71 were males and 24 females. The other half of Group I was composed of 95 cases (CS) of cervical spondylosis of the same sex and age distribution. Group II comprised 189 cases, all males aged 49 yrs. Of them, 41 were OPLL cases, 102 CS, and 46 normal subjects. The X-ray films of Group II were taken during medical examinations. The height, antero-posterior diameter of the cervical vertebral bodies and the antero-posterior diameter of the cervical spinal canals were measured and examined for kyphosis between the two neighbouring cervical vertebral bodies, disc space narrowing and Barsony ossification. The height and antero-posterior diameter of the cervical vertebral bodies were compared among the following groups. 1) the 3 groups divided according to age (-49,50-59,60-75 yrs.), 2) segmental type with non-segmental type, 3) OPLL only at C3 and C4 with OPLL only at C5, C6, and C7. The results were as follows: The cervical vertebral bodies of OPLL were taller and wider than those of CS. Cervical vertebral bodies of the older group were shorter and wider than those of the younger groups in both OPLL and CS. THe relative height (C3 = I) of OPLL group was very close to Normal group. The cervical vertebral bodies of non-segmental type were taller but not wider than those of segmental type of OPLL group. The C3 and C4 vertebral bodies with OPLL only at C3 and C4 were taller, but not wider than those with OPLL only at C5, C6 and C7. The antero-posterior diameter of cervical spinal canal of OPLL was narrower than CS group. The above data indicate the following: 1) With advance in age, cervical vertebral bodies become lower and wider. 2) The cervical vertebral body of OPLL is taller and wider than that of CS. 3) The level of OPLL and the type of OPLL have a relation to the height of cervical vertebral body. 4) The cervical vertebral bodies which have OPLL are wider than non-OPLL. But the level and the type of OPLL have no relation with the A-P diameter of the cervical vertebral body.

Adult↗
PubMed1981

[Experimental study of cervical spondylotic myelopathy--spinal cord blood flow in cervical canal stenosis (author's transl)].

There exists the view that ischemia in the spinal cord accounts for the paralysis caused by cervical spondylotic myelopathy (CSM), but little work has been done to study the change of spinal cord blood flow (SCBF) in CSM. To clarify this situation, the experimental model designed by Tanaka (1978) was used as a model of CSM (Fig. 1). Among 27 cats in which the spinal canal was narrowed between C4 and C6, 13 cats developed delayed paralysis 33 weeks after operation in an average. Spinal cord blood flow was measured by the reference sample method using isotopelabeled microspheres of 15 +/- 3 mu in diameter. The mean SCBF values for each spinal segments in normal animals ranged from 23.0 g/min . 100 g in T11 to 40.2 g/min . 100 g in C8, resulting in that blood flow in the cervical and lumbar enlargements was constantly higher than that in the other regions of the cord (Fig. 3). The mean blood flow values for the gray matter, ventral white matter, lateral white matter, and dorsal white matter in cervical region were 99.1, 5.0, 5.9, and 11.4 g/min . 100 g respectively, without significant difference between each spinal segments (Fig. 4). In an animal with acute spinal cord compression, the SCBF decreased significantly 15 minutes after spinal cord compression was induced (Figs. 5, 6). On the other hand, in two delayed paralysis animals SCBF in the narrowed segments was within normal limits (Figs. 5, 6). These results suggest that paralysis as seen in CSM may develop without ischemia of the spinal cord.

Animals↗
PubMed1980

Interferon production in human diploid cell strains derived from embryonic lungs.

Twenty-three strains of human diploid cells derived from embryonic lungs were tested for production of interferon by "superinduction." Strain HAIN-55 produced a relatively high level of interferon. The optimal concentration of cycloheximide for superinduction was essentially equal to that reported with foreskin fibroblasts. On the other hand, actinomycin D at a concentration of 4 to 16 microgram/ml enhanced the production of interferon more strikingly than at a concentration of 1 microgram/ml, which was usually employed for superinduction in the foreskin fibroblasts. Inhibition of interferon production was observed when fetal bovine serum was added to the medium during treatment with metabolic inhibitors for superinduction. Minimal essential medium was superior to Eagle's basal medium as growth medium for interferon production, and serum added after removal of metabolic inhibitors could be replaced by bovine serum albumin. The yield of interferon produced under the best conditions in this study, with strain HAIN-55, was more than 10,000 reference units/ml.

Blood↗
PubMed1980

Susceptibility of influenza viruses to interferon and to poly(I) . Poly(C) determined by the plaque reduction method.

Susceptibility of eight strains of influenza A and B viruses to interferon and to poly(I) . poly(C) were determined by the plaque reduction method. All strains tested were slightly less susceptible than vesicular stomatitis virus (VSV) in an established line of canine kidney (MDCK) cells. The 50% plaque depression doses (PD50) of poly(I) . poly(C) for influenza A and B viruses were as high as 3.0- to 4.5-fold and 6- to 18-fold that for VSV, respectively. The amounts of interferon required to inhibit plaque formation of influenza A and B viruses by 50% were 3.0-6.2 and 7.3-15.2 units/ml, respectively. The ratio of PD50 of poly(I) . poly(C) for each strain of influenza viruses tested to that for VSV in chick embryo cells was almost the same as in MDCK cells. Furthermore, in chick embryo cells, the strains of influenza virus tested were demonstrated to be much more susceptible to poly(I) . poly(C) than both Newcastle disease virus and vaccinia virus. It is suggested that influenza viruses may be relatively susceptible to interferon and to poly(I) . poly(C).

Animals↗
PubMed1980

Effect of treatment with 1-beta-D-arabinofuranosylthymine of experimental encephalitis induced by herpes simplex virus in mice.

1-beta-D-Arabinofuranosylthymine (ara-T) was examined for its therapeutic efficacy against encephalitis in mice inoculated intracerebrally with herpes simplex virus. Intraperitoneal treatment with 100 mg of ara-T per kg twice daily for 4.5 days was as effective as treatment with 50 mg of arabinosyladenine 5'-monophosphate per kg. Under the same conditions, doses of 5-iododeoxyuridine or arabinosylcytosine (50 mg/kg each) were not effective. Even when the virus inoculum was as high as 320 or 3,200 50% lethal doses, ara-T increased the life span significantly. Oral treatment with 27 mg of ara-T per kg produced a modest increase in the mean survival time, equal to that of 50 mg of ara-T per kg administered intraperitoneally or subcutaneously. A single dose of ara-T, 800 mg/kg intraperitoneally or 400 mg/kg orally, was effective. The 50% lethal dose of ara-T administered intraperitoneally and that administered orally were more than 10 and 15 g/kg, respectively. The therapeutic indexes (maximal tolerated dose divided by minimal effective dose) in multiple intraperitoneal treatments and in multiple oral treatments were estimated to be more than 25 and 100, respectively.

Animals↗