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Biomedical subjects

H Ohmori

Publications and source records attributed to H Ohmori.

At least 415 records · Page 23Linked to original sources

The relationship between age-dependent immunological competence of host and tumor growth in the hamster-bovine adenovirus type 3 system.

The relationship of aging to carcinogenesis was immunologically examined in the hamster-bovine adenovirus type 3 system. The age of animals at the time of virus inoculation influenced the tumor growth and latency period, but not the tumor incidence. The immunological competence of hamsters to sheep red blood cells became matured around 4 weeks after birth and was not affected by the infection of bovine adenovirus type 3 (BAV-3). The strength of transplant immunity was dependent on the age of animals at the time of immunization. The growth of progressive type of tumors induced by inoculation with BAV-3 into younger animals was inhibited by the repeated inoculation of excess dose of BAV-3, administration of BCG and transfer of sensitized lymphocytes during the tumor latency. The growth of non-progressive type of tumors induced by inoculation with BAV-3 into adult hamsters was accelerated by administration of antithymocyte serum or thymectomy. The tolerance to tumor specific transplantation antigens did not play a critical role in the present system. The blocking activity to sensitized lymphocytes was demonstrated in the sera taken from hamsters developing a progressive type of tumor even in the early period of carcinogenesis.

Adenoviridae↗

Extrarenal renin-secreting tumor associated with hypertension.

Described herein is an autopsy case of a 16-year-old female with severe hypertension, hyperreninemia and secondary aldosteronism. She had had a progressively growing tumor of her right orbita from the age of 4. The tumor was partially excised 13 months before death. A high content of a renin-like material was detected in the excised tumor, which was histologically a hemangiopericytoma. Bowie stain revealed some granules in small number of tumor cells and electron microscopic study showed some cytoplasmic granules. Following the operation, hypertension was somewhat improved, but the levels of plasma renin activity and plasma aldosterone concentration remained elevated, because the tumor was partially resected. At autopsy, the tumor invaded into the cranial base and right frontal lobe, and metastasized to the lungs. In the present case, renal renin-secreting tumor, malignant hypertension and renovascular hypertension were ruled out by the clinical and pathological studies.

Adolescent↗

Surface potential reflected in both gating and permeation mechanisms of sodium and calcium channels of the tunicate egg cell membrane.

1. Threshold changes of Na and Ca currents due to various polyvalent cations (stabilizing cations) or H(+) ions were studied in the egg cell membrane of a tunicate, Halocynthia roretzi, by using the voltage-clamp technique.2. With an increase in [Ca](o) or a decrease in pH in the external solution, the current-voltage (I-V) relations for the peak of the Na and Ca currents shifted along the voltage axis in the positive direction. These voltage shifts in the I-V relations, measured at a potential of V((1/2)) where inward current attains its half-maximum, were shown to be identical to shifts in voltage-dependence of the time courses of Na and Ca currents, and also identical to shifts in the inactivation curves of Na current along the voltage axis.3. The shifts in V((1/2)) produced by various polyvalent cations or H(+) ions were analysed by the Gouy-Chapman equation for the diffuse double layer, by assuming that a change in V((1/2)) directly corresponds to a change in the surface double layer potential.4. The V((1/2))-divalent cation concentration relations of Na current were exactly described by the predictions of the theory with a constant value of the surface charge density of 1e(-)/(9 A)(2). The weak stabilizing effects of Mg(2+), Sr(2+) and Ba(2+) were quite similar to each other and were explained in terms of a ;screening' effect. Other divalent cations, such as Ca(2+), Mn(2+) and Ni(2+), showed various different stabilizing effects which were explained in terms of a ;binding' effect. The binding constants (K(1)'s) for Ca(2+), Mn(2+) and Ni(2+) were 0.21, 0.45 and 0.94 M(-1), respectively.5. H(+) ions showed a powerful stabilizing effect upon the Na current with a K(H) of 6 x 10(4)M(-1). This value indicates that the acidic sites around Na channels have a pK(a) of 4.78. La(3+) ions also acted as a strong stabilizer upon the Na current with a K(La) of 15 M(-1). For both H(+) and La(3+), the V((1/2))-concentration relations were also exactly described by the Gouy-Chapman equation with the same charge density of 1e(-)/(9 A)(2) as estimated by varying divalent cations.6. The stabilizing effect of permeant cations such as Ca(2+), Sr(2+) and Ba(2+) on Ca channel currents was analysed. The effect of lowering pH was also studied. It was found that the surface charge density of 1e(-)/(9 A)(2) estimated by Na current is also applicable to the explanation for the V((1/2))-divalent cation concentration or - pH relationships. The estimated binding constants for H(+), Ca(2+) and Sr(2+) were 1.2x10(5), 0.58 and 0.035 M(-1), respectively. Ba(2+) does not bind to charged sites near to the Ca channels.7. It was noticed that a considerable reduction in the conductances of Na and Ca currents occurred in parallel with a stabilizing effect. This reduction was ascribed to a decrease in the concentration of permeant cations at the external surface of the cell membrane, as predicted by the theory of the diffuse double layer. The Goldman, Hodgkin-Katz equation for ionic currents was applied to explain the conductance suppression.8. The conductance suppressions of Na and Ca channel currents due to Ca(2+), Sr(2+) and Ba(2+) were found to be apparent ones, only reflecting decreases in the surface concentration of permeant cations without any changes in the permeability. After correction for the apparent suppression, the real permeability ratio among Ca(2+), Sr(2+) and Ba(2+) for Ca channels was determined as 1.00, 0.56 and 0.21 respectively.9. The conductance suppression of Na current by lowering pH was explained in terms of a real suppression or blocking which is superimposed on the apparent suppression. Considering the surface [Na](o), the plot of P(Na) against the surface pH yielded a blocking curve of Na channel by H(+) ions, which implies that two H(+) ions are necessary to block each Na channel. For Ca channels no real blockage was observed in acidic pH.10. It was concluded from the present experiment that there exists a surface potential capable of affecting both gating and permeation mechanisms of ionic channels in this tunicate egg cell membrane.

Animals↗

Development of neuromuscular transmission in a larval tunicate.

1. The time sequence of the development of acetylcholinesterase (AChE), acetylcholine (ACh) receptors and functional synapses on the embryonic muscle membrane in a tunicate larva (Halocynthia roretzi) was investigated in vivo.2. The fertilized tunicate egg was incubated in natural sea water at 9 degrees C. Sixty-eight hr after fertilization the free-swimming larva was hatched, which had six striated muscle fibres in the tail. The developmental stage of the embryo was indicated by the developmental hours after fertilization.3. The transmitter at the neuromuscular junction in the hatched larva is ACh. (i) Neuromuscular transmission was completely blocked by D-tubocurarine (1-5 x 10(-5)M). (ii) Eserine (5-10 x 10(-7)M) approximately doubled the time constant of the falling phase of miniature excitatory junctional currents (e.j.c.s). (iii) The reversal potential of the membrane response to iontophoretically applied ACh was -10 mV and similar to that of e.j.c.s. (iv) AChE was present on the muscle membrane surface.4. AChE activity became visible histochemically on the embryonic cell membrane in the presumptive muscle region as early as the late gastrula stage (27 hr after fertilization, 12 hr before the ACh response appeared).5. The response to iontophoretically applied ACh was present at 39 hr after fertilization but could not be evoked at 38 hr.6. Between 39 and 41 hr after fertilization, the ACh responses increased rapidly, then remained relatively unchanged until larval hatching.7. The stage of the initial appearance of the ACh response corresponded to the stage when the Ca current abruptly increased in the muscle membrane.8. The first sign of neuromuscular transmission was appearance of a giant excitatory junctional potential (e.j.p.) with uniform amplitude (about 15-20 mV) and slow time course (time constant of the falling phase of a giant e.j.c. was 23.4 +/- 6.9 msec, mean and S.D., at -60 mV and 11 degrees C).9. Within a few hours, these giant e.j.p.s disappeared and were successively replaced by medium-sized e.j.p.s and then e.j.p.s similar to those seen in hatched larvae (time constant of the falling phase of a miniature e.j.c. was 8.5 +/- 1.8 msec at -60 mV and 11 degrees C).

Acetylcholine↗

Factors involved in beta-lactam antibiotic resistance in Pseudomonas aeruginosa.

A temperature-sensitive mutant, strain SS, which is assumed to be devoid of beta-lactamase activity and deficient in a permeability barrier to antibiotics, was isolated from a beta-lactamase-less mutant, strain L-2, derived from Pseudomonas aeruginosa IFO 3080. By comparing the beta-lactam antibiotic susceptibility between strains IFO 3080, L-2, and SS, the involvement of both beta-lactamase and a permeability barrier in determining the beta-lactam antibiotic resistance was estimated.

Anti-Bacterial Agents↗

Effect of exercise on alimentary lipemia in healthy men.

To investigate the effect of exercise on alimentary lipemia, 6 healthy volunteers were exmained for their plasma parameters successively for 6 hr after ingestion of emulsified butter (1 g/kg body weight) with and without subsequent intermittent loading of exercise (720 kilopound meters per min for 2 min, 6 times at hourly intervals) using a bicycle ergometer. No apparent differences were found between the fat loading test and the fat and exercise loading test in the 6 hr levels of plasma chylimicron-triglyceride, lipoprotein-triglyceride and endogenous lipolytic activity measured by the usual lipoprotein lipase assay method, although the increase in plasma free fatty acids in the fat and exercise loading test was significantly greater than that in the single fat loading test. It is concluded that the intermittent muscle exercise adopted in this study has no significant inffuence on the triglyceride elevation after the fat loading in man.

Adolescent↗

Mechanism of inhibition of Chromatium D growth by L-methionine. Regulation of L-threonine biosynthesis by the intracellular level of S-adenosylmethionine.

(1) An unusual accumulation of S-adenosyl-L-methionine in Chromatium D was associated with a marked growth inhibition by L-methionine. The inhibition was overcome by L-isoleucine, L-leucine, L-phyenylalanine, L-threonine, L-valine and putrescien. Based on their effects, these compounds are classified into 3 types. (2) L-Isoleucine, L-leucine, L-phyenylalanine and L-valine (Type I) inhibited the L-methionine uptake and consequently prevented the bacterium from the unusual accumulation of S-adenosyl-L-methionine even in the presence of L-methionine in the medium. Putrescine (Type II) stimulated the consumption of S-adenosyl-L-methionine, but did not influence the L-methionine uptake. Hence, the effect of putrescine would be explained by the action to diminish the intracellular level of S-adenosyl-L-methionine. L-Threonine (Type III) neither inhibited the L-methionine uptake nor affected the content of S-adenoxyl-L-methionine due to the addition of L-methionine. (3) The specific activity of homoserine kinase (EC 2.7.1.39) was greatly lowered by the addition of L-methionine under conditions in which Chromatium D unusually accumulates S-adenoxyl-L-methionine. Homoserine dehydrogenase (EC 1.1.1.3) activity was inhbitied by S-adenosyl-L-methionine (50% inhibition index, 3.5 mM). These facts strongly suggest that the growth inhibition by L-methionine is associated with the L-threonine deficiency caused by the unusual accumulation of S-adenosyl-L-methionine.

Amino Acids↗

Action potential and non-linear current-voltage relation in starfish oocytes.

1. The electrical properties of the oocyte membrane of the starfish, Asterina pectinifera, were investigated using an intracellular microelectrode. 2. The resting potential in artificial sea-water ranged from -70 to -80 mV. 3. The starfish oocyte membrane was capable of generating an action potential as a result of permeability increases to both Ca and Na ions.4. The Ca component of the action potential was reversibly suppressed by Co or Mg ions, while the Na component was not affected by tetrodotoxin 5 times 10-minus 6 g/ml. 5. The steady-state relation of voltage vs. current was not linear but S-shaped. The curve wascomposed of inward-going rectification at the membrane potential more negative than -65 mV, outward-going rectification at the potential more positive than OmV and the transitional region between them. These findings are compared with those obtained in the mature egg of the tunicate.

Action Potentials↗

Potassium rectifications of the starfish oocyte membrane and their changes during oocyte maturation.

1. The current-voltage relations of the oocyte membrane of the starfish, Asterina pectinifera, and their changes during maturation were investigated using current-clamp techniques. 2. The resting potential of the oocyte membrane in sea water was found to be determined by the diffusion potential of K ions. 3. In the absence of Na and Ca inward currents the steady-state current-voltage relation of the oocyte membrane had inward-going K rectification at membrane potentials more negative than -65 mV and outward-going K rectification at potentials more positive than -30 mV, forming a S-shaped I-V curve. 4. A negative resistance region of the steady-state I-V curve was revealed with voltage-clamp technique in the potential range between -65 and -30 mV. 5. Transient K activation occurred when the membrane was brought from a resting potential of about -75 mV to potentials more positive than -20 mV, and this was immediately followed by K inactivation. Accordingly, the steady-state I-V relation showed only slight outward-going rectification. 6. At the beginning of meiosis, which is signalled by break-down of the nucleus, the limiting slope conductance in the inward rectifying region of the I-V curve decreased sevenfold. The cell membrane lost its selective permeability to K ions and was depolarized from -70 to between -20 and OmV in standard artificial sea-water. The depolarized resting potential was partly due to the relative increase in Na permeability. K conductance began to increase again within 30 min after breakdown of the nucleus. The resting potential became gradually larger and eventually attained -70 mV in the mature egg. 7. In the mature egg, K activation upon depolarization was no longer followed by inactivation. Accordingly, the slope conductance in the outward rectifying region of the I-V curve increased. 8. The action potential was augmented at the stage of nuclear breakdown. Thereafter the maximum rate of rise decreased and the duration of the action potential shortened. These changes were caused primarily by changes in K conductance during maturation. 9. Fertilization of the egg during the maturation process did not affect the changes in the I-V relation described above, except for a transient change of the membrane permeability upon fertilization.

Action Potentials↗

In vitro studies on target cells of oncogenic adenoviruses in hamster brain. II. In vitro transformation of brain cells of hamsters at various ages by human adenovirus type 12.

In vitro transformations of brain cells of hamsters of various ages were examined after the administration of human adenovirus type 12 (Ad 12) to determine the type and origin of the target cell. Hamster brain cells at all examined ages were transformed by Ad12. Although the virus was not isolated, virus specific tumor antigen was demonstrated in the transformed cells. The histological features of tumors that developed by transplantation of transformed cells closely resembled Ad12-induced brain tumors. The transformed cell focus tended to appear near the embryonic brain cell (EB cell) or glioblastic cell (GB cell). The transformed cells were morphologically similar to the EB or GB cell. Some subcultured transformed cells showed a rosette-like pattern, and the surrounding space arrangement was similar to that of the ventricular wall. The incidence of brain cell transformations decreased with increased hamster age. This decreased incidence with age corresponded to the decreased numbers of EB or GB cells present in progressively older hamsters. From these results, it is concluded that the target cells of AD12 in hamster brain cell cultures are probably the EB or GB cells.

Adenoviridae↗

In vitro studies on target cells of oncogenic adenoviruses in hamster brain. III. In vitro transformation of brain cells of hamsters at various ages by bovine adenovirus type 3.

In vitro transformation of brain cells of hamsters at various ages was examined after the addition of bovine adenovirus type 3 to determine the type and origin of the target cells. Cellular transformations occurred only in cultures of fetus and newborn animals and at low incidences. Nine cell lines were obtained. Virus specific tumor antigens were demonstrated in the transformed cells. The present investigation suggested that bovine adenovirus type 3 might transform mesenchymal cells (ME cell) and that these cells are probably of meningeal or vascular origin. The histological picture of tumors following transplantation of the transformed cells resembled human primary sarcoma of the meninges and brain.

Adenoviridae↗

In vitro antigen-specific IgE response is refractory to suppression by interferon-gamma.

Although interferon (IFN)-gamma has been shown to be involved in the down-regulation of polyclonal IgE response in murine B cells that were activated by lipopolysaccharide (LPS) and interleukin 4 (IL4), effects of IFN-gamma on antigen-specific IgE responses have not been fully investigated. We have developed the following culture systems for inducing antigen-specific IgE responses in murine lymphocytes, and examined the effects of IFN-gamma on the following responses in vitro. (1) Anti-trinitrophenyl (TNP) IgE response induced by the stimulation with TNP-keyhole limpet hemocyanin (KLH) of BALB/c spleen cells that had been primed in vivo with the same antigen. (2) Anti-TNP IgE response induced by the coculture of unprimed C3H B cells with conalbumin (CA)-specific helper T cell clone, D10.G4.1, in the presence of TNP-CA. The former anti-TNP IgE response was not suppressed, and the latter suppressed only partially (less than 30%) by the addition of 100-200 U/ml IFN-gamma. In contrast, polyclonal IgE response in murine B cells that were stimulated by LPS and IL4 was abolished by 10 U/ml IFN-gamma. These results indicate that IgE production from antigen-stimulated B cells, in contrast to those activated polyclonally, are refractory to direct suppression by IFN-gamma.

Animals↗

Induction of antigen-specific IgE response in murine lymphocytes by IL-10.

When murine spleen cells that had been primed with trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH) were stimulated in vitro with the same antigen, anti-TNP IgE, as well as anti-TNP IgM and IgG1, was secreted into the culture medium. On the other hand, anti-TNP IgM and IgG1 were produced, but anti-TNP IgE secretion was negligible when the carrier (KLH)-primed spleen cells were cultured with the hapten-carrier antigen (TNP-KLH) under the same conditions. Anti-TNP Ig responses in the latter cultures are thought to reflect the interaction between normal TNP-specific B cells and KLH-primed helper T cells. By using this culture system, we investigated the requirements of exogenous cytokines for inducing anti-TNP IgE response. The addition of interleukin-4 (IL-4), that is known to induce IgE response in LPS-stimulated murine B cells, failed to elicit anti-TNP IgE response. The combination of IL-4 with IL-2 and/or IL-5 was also ineffective. Interestingly, a significant level of anti-TNP IgE was induced when IL-10, another cytokine from type 2 helper T cells, was added to the culture. Although IL-10 enhanced the production of anti-TNP IgM and IgG1, as well as that of anti-TNP IgE, the rate of enhancement was at least 3-fold higher in the IgE response than in the IgM and IgG1 responses. Simultaneous addition of IL-4, IL-5 or IL-13 with IL-10 did not augment but rather reduced the enhancing effects of IL-10. IL-10 did not further stimulate the spontaneous secretion of IgE from antigen-primed B cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neurotoxicity of phenytoin administered to newborn mice on developing cerebellum.

To examine the neurotoxic effects of phenytoin (PHT) on cerebellar development, we administered 50 mg/kg PHT suspended in sesame oil orally to newborn Jcl:ICR mice once a day during postnatal days 2-14 and determined plasma PHT concentrations at designated intervals during the administration period. In the treated group, walking reflex and negative geotaxis were poorly developed on postnatal day 14. Pyknotic cells in the external granular layer (EGL) significantly increased and were prominent in the vermis area compared with controls on postnatal day 14. Plasma PHT levels were 34-36 micrograms/ml on the 3rd day of PHT treatment and approached a steady-state situation. Total brain weight, size of the cerebellum, and cerebellar weight were significantly reduced in the treated group on postnatal day 56. Accordingly, oral administration of PHT in the neonatal period induced neurotoxic damage on the developing cerebellum.

Animals↗

Effects of low-dose phenytoin administered to newborn mice on developing cerebellum.

To examine correlations between dose levels of phenytoin (PHT) and neurotoxic effects on cerebellar development, we administered 10, 17.5, 25, and 35 mg/kg PHT suspended in sesame oil orally to newborn Jcl:ICR mice once a day during postnatal days 2-4 and determined plasma PHT concentrations during the administration period. Mortality rates were 12.5% and 35.2% in males and 15.3% and 33.3% in females for the 25 and 35 mg/kg PHT-treated groups during the PHT treatment, respectively. In the 25 and 35 mg/kg PHT-treated groups, total brain weight, the size of the cerebellum, and cerebellar weight were significantly reduced on postnatal day 21. However, in the 10 and 17.5 mg/kg PHT-treated groups, total brain weight and the size and weight of the cerebellum did not differ from those of the control group. Histologically, the number of pyknotic cells in the external granular layer (EGL) in the 25 and 35 mg/kg PHT-treated groups was increased on postnatal day 5, and the EGL was thicker than in the control group on postnatal day 14. Some of the Purkinje cells in the 35 mg/kg PHT-treated group showed degeneration. Plasma PHT levels were 10.7 +/- 2.2 and 24.6 +/- 2.6 micrograms/ml in the 25 and 35 mg/kg PHT groups on the third day of PHT treatment, respectively. In the 25 mg/kg PHT group, plasma PHT level was found to be in the therapeutic range for humans, 10-20 micrograms/ml. Accordingly, during pregnancy, epileptic women should be carefully given PHT at the lowest effective dose while plasma PHT levels are monitored properly. These findings emphasize the importance of pharmacokinetics in evaluating of phenytoin-induced developmental neurotoxicity.

Animals↗

Neurotoxic effects of phenytoin on postnatal mouse brain development following neonatal administration.

Phenytoin (PHT) is a commonly used anticonvulsant drug. It has been reported that children exposed prenatally to PHT have brain malformations and psychomotor dysfunction. The neonatal development of the central nervous system (CNS) in mice corresponds to the last trimester in humans. To examine the neurotoxic effects of PHT on postnatal brain development, we administered PHT at doses of 10, 17.5, 25, or 35 mg/kg to newborn mice once a day during postnatal days (PD) 2-4. These dose levels result in plasma levels corresponding to the therapeutic ranges in humans. We measured the weight of total brain, cerebrum, cerebellum, and brain stem on PD 5 through 21, and examined early motor functions including head elevation, elevation of pelvis, pivoting, crawling, and righting reflex . Total brain weight, cerebral weight, and cerebellar weight in the group treated with 25 or 35 mg/kg were significantly reduced compared to controls from PD 5 to 21. Mice treated with PHT at 25 or 35 mg/kg showed decreased locomotor abilities and righting reflex on PD 5. In all phenytoin treatment groups, phenytoin levels in the brain were higher than those in the plasma on the third day of PHT treatment. We thus observed neurotoxic effects of PHT on postnatal brain development in mice. Our present data may provide useful implications for the management of PHT-induced developmental neurotoxicity and evaluation of psychomotor development in children exposed to PHT during the late fetal period.

Aging↗